Attorney Docket: 51771-0003WO1 ALPHA 2 MACROGLOBULIN, SOLUBLE KLOTHO AND METHODS OF USE THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of priority of U.S. Provisional Application No. 63/416,734, filed October 17, 2022, U.S. Provisional Application No.63/443,830, filed February 7, 2023, and U.S. Provisional Application No.63/451,381, filed March 10, 2023, the content of each of which are incorporated by reference in their entirety herein. SEQUENCE LISTING [0002] This application contains a Sequence Listing that has been submitted electronically as an XML file named 51771-0003WO1_SL_ST26.xml. The XML file, created on October 12, 2023, is 39,731 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety. FIELD [0003] The present disclosure relates generally to alpha 2 macroglobulin (A2M) protein and soluble Klotho (sKL) protein, compositions comprising same, and related uses (e.g., treating a coronavirus (e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, treating post-acute sequelae (PASC), treating inflammation, treating cognitive decline (e.g., Alzheimer’s disease), improving cognition, inhibiting senescence, treating bacterial infection, inhibiting an interaction between a SARS-CoV-2 spike protein and an angiotensin-converting enzyme 2 (ACE2) protein, inhibiting a coronavirus (e.g., SARS-CoV-2) papain-like protease (PLpro) protein, rejuvenating skin, and cosmetically treating skin). BACKGROUND OF THE INVENTION [0004] Alpha 2 Macroglobulin (A2M) functions as a broad-spectrum protease-binding protein, which acted as a major component of the innate immune system, and has a dual role as a pan- protease inhibitor and a scavenger protein. More recently, it has been reported that numerous growth factors, cytokines and hormones bind to A2M through diverse mechanisms. It is a highly Attorney Docket: 51771-0003WO1 abundant protein that can interact with a range of molecules, resulting in its ability to influence many biological processes such as cytokine clearance and the opsonization of bacteria. There is evidence to suggest that A2M may have an important role in the neuro-inflammatory response to Alzheimer’s disease (AD) pathogenesis (Varma et al., Mol Psychiatry. (2017) 22:1; Wu et al., J Immunol. (1998) 161(8):4356-65). [0005] Klotho, also called Klotho-α, is the founding member of the Klotho family within the glycosidase-1 superfamily (Nabeshima Y, Imura H. Sci. Aging Knowl. (2008) 28:455-464; Kuro-o, M. et al., Nature. (1997) 390 (6655):45-51). Klotho is expressed in areas concerned with calcium regulation, predominantly in the kidney distal convoluted tubules, but also in the brain choroid plexus (which produces cerebrospinal fluid) and the parathyroid (Nabeshima Y, Imura H. Sci. Aging Knowl. (2008) 28:455-464). The phenotype of Klotho-deficient mice resembles premature aging, including arteriosclerosis, osteoporosis, skin atrophy, infertility, emphysema and premature death (Kuro-o, M. et al., Nature. (1997) 390 (6655):45-51). [0006] Klotho exists in two main forms: full-length transmembrane Klotho and soluble Klotho, the latter being formed by proteolytic cleavage of membrane Klotho. The role of soluble Klotho in disease and repair is not fully understood. Emerging evidence suggest that soluble Klotho exhibits humoral activity as Klotho deficient mice have functional deficits in organs which do not express Klotho. Other reports demonstrate that soluble Klotho may act as an on-demand co- receptor for fibroblast growth factor 23 (FGF-23) or it may act independently of FGF23 and interact with monosialogangliosides in lipid rafts of the plasma membrane, altering their lipid organization and modulating biological pathways that regulate oxidative stress, apoptosis, stem cell renewal, fibrogenesis and angiogenesis. Soluble Klotho reduces oxidative stress by promoting forkhead transcription factor activation and nuclear translocation, leading to upregulation of manganese superoxide dismutase (MnSoD). It also suppresses fibrosis by binding to type II transforming growth factor-beta 1 (TGF-β) receptor, preventing TGF-β binding and inhibiting SMAD 2/3 signaling (Sunil B et al., Scientific Reports (2020) 10:12368; Kurosu, H. et al., Science (2005) 309:1829–1833). [0007] The coronavirus disease 2019 (COVD-19), caused by the novel SARS-CoV-2 resulted in a global public health crisis and pandemic, shining a light on the unmet need for new treatments for microbial infections and inflammation. Attorney Docket: 51771-0003WO1 SUMMARY OF THE INVENTION [0008] This disclosure provides A2M proteins and sKL proteins and compositions comprising the same and related methods of making same, polynucleotides, vectors, and cells. This disclosure also provides compositions (e.g., pharmaceutical compositions) comprising both an A2M protein and an sKL protein. [0009] This disclosure is based, in part, on the surprising discovery that A2M and sKL act synergistically with each other, despite not directly binding to each other. In particular, the working examples herein demonstrate that A2M and sKL exhibit an enhanced antiviral effect against SARS-CoV-2 and its variants. A2M and sKL, alone and in combination, also reduce the inflammatory response in models of inflammation and bacterial infection. The working examples also demonstrate that A2M and sKL inhibit cathepsin L significantly and the interaction between the SARS-CoV-2 spike protein and its receptor, ACE2, and synergize to inhibit SARS-CoV-2 PLpro. The working examples also demonstrate that A2M targets 3- CLpro/Mpro of SARS-CoV-2 by unexpectedly increasing hydrolysis in a dose-dependent manner, which without being bound by any particular theory, indicates increased “cutting” of the virus – thus preventing any lengthening or maturation of the virus RNA, rendering it effectively redundant. [0010] Provided herein is a pharmaceutical composition, comprising: a therapeutically effective amount of an A2M protein, a therapeutically effective amount of an sKL protein, and a pharmaceutically acceptable carrier. In some instances, the A2M protein and sKL protein are present in the pharmaceutical composition in a stoichiometric ratio of A2M:sKL of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. In some instances, the A2M protein is human A2M protein. In some instances, the sKL protein is human sKL protein. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:6. In some instances, the A2M protein is in dimeric form. In some instances, the sKL protein comprises a phenylalanine at the amino acid corresponding to position 12 of SEQ Attorney Docket: 51771-0003WO1 ID NO:15. In some instances, the sKL protein comprises the amino acid sequence set forth in SEQ ID NO:15. [0011] Also provided herein is a method of treating a coronavirus infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein and a therapeutically effective amount of an sKL protein. In some instances, the coronavirus infection is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered at a stoichiometric ratio of A2M:sKL of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as a single composition. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as two separate compositions. In some instances, the two separate compositions are administered sequentially. In some instances, the two separate compositions are administered simultaneously. In some instances, the subject is a human. [0012] Also provided herein is a method of treating a coronavirus infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein. In some instances, the coronavirus infection is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In some instances, the subject is a human. [0013] Also provided herein is a method of treating a coronavirus infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein. In some instances, the coronavirus infection is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In some instances, the subject is a human. [0014] Also provided herein is a method of treating post-acute sequelae SARS-CoV-2 infection (PASC) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein and a therapeutically effective amount of an sKL protein. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered at a stoichiometric ratio of A2M:sKL of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. Attorney Docket: 51771-0003WO1 In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as a single composition. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as two separate compositions. In some instances, the two separate compositions are administered sequentially. In some instances, the two separate compositions are administered simultaneously. In some instances, the subject is a human. [0015] Also provided herein is a method of treating post-acute sequelae SARS-CoV-2 infection (PASC) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein. In some instances, the subject is a human. [0016] Also provided herein is a method of treating post-acute sequelae SARS-CoV-2 infection (PASC) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein. In some instances, the subject is a human. [0017] Also provided herein is a method of treating inflammation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein and a therapeutically effective amount of an sKL protein. In some instances, the inflammation is caused by endotoxin or a bacterial infection. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered at a stoichiometric ratio of A2M:sKL of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as a single composition. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as two separate compositions. In some instances, the two separate compositions are administered sequentially. In some instances, the two separate compositions are administered simultaneously. In some instances, the subject is a human. [0018] Also provided herein is a method of treating inflammation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein. In some instances, the inflammation is caused by endotoxin or a bacterial infection. In some instances, the subject is a human. Attorney Docket: 51771-0003WO1 [0019] Also provided herein is a method of treating inflammation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein. In some instances, the inflammation is caused by endotoxin or a bacterial infection. In some instances, the subject is a human. [0020] Also provided herein is a method of treating cognitive decline in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein and a therapeutically effective amount of an sKL protein. [0021] Also provided herein is a method of treating cognitive decline in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein. [0022] Also provided herein is a method of treating cognitive decline in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein. [0023] Also provided herein is a method of treating Alzheimer’s disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein and a therapeutically effective amount of an sKL protein. [0024] Also provided herein is a method of treating Alzheimer’s disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein. [0025] Also provided herein is a method of treating Alzheimer’s disease in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein. [0026] Also provided herein is a method of improving cognition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein and a therapeutically effective amount of an sKL protein. Attorney Docket: 51771-0003WO1 [0027] Also provided herein is a method of improving cognition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein. [0028] Also provided herein is a method of improving cognition in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein. [0029] Also provided herein is a method of inhibiting senescence in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein and a therapeutically effective amount of an sKL protein. [0030] Also provided herein is a method of inhibiting senescence in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein. [0031] Also provided herein is a method of inhibiting senescence in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M sKL protein. [0032] In some instances of the foregoing methods of treatment, the administering is intranasal. In some instances of the foregoing methods of treatment, the administering is subcutaneous. In some instances, the subject is a human. [0033] Also provided herein is a method of rejuvenating skin in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein and a therapeutically effective amount of an sKL protein. In some instances, the administering is topical administering. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered at a stoichiometric ratio of A2M:sKL of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as a single composition. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as two separate Attorney Docket: 51771-0003WO1 compositions. In some instances, the two separate compositions are administered sequentially. In some instances, the two separate compositions are administered simultaneously. In some instances, the subject is a human. [0034] Also provided herein is a method of rejuvenating skin in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein. In some instances, the administering is topical administering. In some instances, the subject is a human. [0035] Also provided herein is a method of rejuvenating skin in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein. In some instances, the administering is topical administering. In some instances, the subject is a human. [0036] Also provided herein is a method of cosmetically treating skin in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein and a therapeutically effective amount of an sKL protein. In some instances, the administering is topical administering. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered at a stoichiometric ratio of A2M:sKL of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as a single composition. In some instances, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as two separate compositions. In some instances, the two separate compositions are administered sequentially. In some instances, the two separate compositions are administered simultaneously. In some instances, the subject is a human. [0037] Also provided herein is a method of cosmetically treating skin in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein. In some instances, the administering is topical administering. In some instances, the subject is a human. [0038] Also provided herein is a method of cosmetically treating skin in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of Attorney Docket: 51771-0003WO1 an sKL protein. In some instances, the administering is topical administering. In some instances, the subject is a human. [0039] Also provided herein is a method of inhibiting an interaction between a SARS-CoV-2 spike protein and an angiotensin-converting enzyme 2 (ACE2) protein, the method comprising contacting a mixture of the SARS-CoV-2 spike protein and the ACE2 protein with an A2M protein and an sKL protein. [0040] Also provided herein is a method of inhibiting an interaction between a SARS-CoV-2 spike protein and an angiotensin-converting enzyme 2 (ACE2) protein, the method comprising contacting a mixture of the SARS-CoV-2 spike protein and the ACE2 protein with an A2M protein. [0041] Also provided herein is a method of inhibiting an interaction between a SARS-CoV-2 spike protein and an angiotensin-converting enzyme 2 (ACE2) protein, the method comprising contacting a mixture of the SARS-CoV-2 spike protein and the ACE2 protein with an sKL protein. [0042] Also provided herein is a method of inhibiting a coronavirus papain-like protease (PLpro) protein, the method comprising contacting the coronavirus PLpro protein with an A2M protein and an sKL protein. [0043] Also provided herein is a method of inhibiting a coronavirus papain-like protease (PLpro) protein, the method comprising contacting the coronavirus PLpro protein with an A2M protein. [0044] Also provided herein is a method of inhibiting a coronavirus papain-like protease (PLpro) protein, the method comprising contacting the coronavirus PLpro protein with an sKL protein. [0045] In some instances of the foregoing methods involving an A2M protein, the A2M protein is human A2M protein. In some instances, the A2M protein comprises of the amino acid sequence set forth in SEQ ID NO:2. In some instances, the A2M protein comprises of the amino acid sequence set forth in SEQ ID NO:4. In some instances, the A2M protein comprises of the amino acid sequence set forth in SEQ ID NO:6. In some instances, the A2M protein is in dimeric form. [0046] In some instances of the foregoing methods involving an sKL protein, the sKL protein is human sKL protein. In some instances, the sKL protein comprises the amino acid sequence set Attorney Docket: 51771-0003WO1 forth in SEQ ID NO:15. In some instances, the sKL protein comprises a phenylalanine at the amino acid corresponding to position 12 of SEQ ID NO:15. [0047] Also provided herein is a method of producing a pharmaceutical composition comprising a therapeutically effective amount of an A2M protein, a therapeutically effective amount of an sKL protein, and a pharmaceutically acceptable carrier, the method comprising: (a) culturing a first host cell comprising a vector or nucleic acid encoding the A2M protein and isolating the A2M protein from the first host cell; (b) culturing a second host cell comprising a vector or nucleic acid encoding the sKL protein and isolating the sKL protein from the second host cell; and (c) combining the isolated A2M protein and sKL protein with the pharmaceutically acceptable carrier. In some instances, the A2M protein and sKL protein are present in the pharmaceutical composition in a stoichiometric ratio of A2M:sKL of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. In some instances, the A2M protein is human A2M protein. In some instances, the sKL protein is human sKL protein. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:6. In some instances, the A2M protein is in dimeric form. In some instances, the sKL protein comprises a phenylalanine at the amino acid corresponding to position 12 of SEQ ID NO:15. In some instances, the sKL protein comprises the amino acid sequence set forth in SEQ ID NO:15. [0048] Also provided herein is a method of producing a pharmaceutical composition comprising a therapeutically effective amount of an A2M protein, a therapeutically effective amount of an sKL protein, and a pharmaceutically acceptable carrier, the method comprising: (a) culturing a host cell comprising a first vector or a first nucleic acid encoding the A2M protein and a second vector or a second nucleic acid encoding the sKL protein; (b) isolating the A2M protein and the sKL protein from the host cell; and (c) combining the isolated A2M protein and sKL protein with the pharmaceutically acceptable carrier. In some instances, the A2M protein and sKL protein are present in the pharmaceutical composition in a stoichiometric ratio of A2M:sKL of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. In some instances, the A2M protein is human A2M protein. In some instances, the sKL protein is human sKL protein. Attorney Docket: 51771-0003WO1 In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:6. In some instances, the A2M protein is in dimeric form. In some instances, the sKL protein comprises a phenylalanine at the amino acid corresponding to position 12 of SEQ ID NO:15. In some instances, the sKL protein comprises the amino acid sequence set forth in SEQ ID NO:15. [0049] Also provided herein is a method of producing a pharmaceutical composition comprising a therapeutically effective amount of an A2M protein, a therapeutically effective amount of an sKL protein, and a pharmaceutically acceptable carrier, the method comprising: (a) culturing a host cell comprising a vector or a nucleic acid encoding the A2M protein and the sKL protein; (b) isolating the A2M protein and the sKL protein from the host cell; and (c) combining the isolated A2M protein and sKL protein with the pharmaceutically acceptable carrier. In some instances, the A2M protein and sKL protein are present in the pharmaceutical composition in a stoichiometric ratio of A2M:sKL of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. In some instances, the A2M protein is human A2M protein. In some instances, the sKL protein is human sKL protein. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence set forth in SEQ ID NO:6. In some instances, the A2M protein is in dimeric form. In some instances, the sKL protein comprises a phenylalanine at the amino acid corresponding to position 12 of SEQ ID NO:15. In some instances, the sKL protein comprises the amino acid sequence set forth in SEQ ID NO:15. [0050] In some instances of the foregoing methods, the therapeutically effective amount of the A2M protein is about 10 mg and the therapeutically effective amount of the sKL protein is about 2.5 mg; the therapeutically effective amount of the A2M protein is about 5 mg and the therapeutically effective amount of the sKL protein is about 1 mg; or the therapeutically effective amount of the A2M protein is about 1 mg and the therapeutically effective amount of the sKL protein is about 0.25 mg. In some instances of the foregoing methods, the therapeutically effective amount of the A2M protein is 10 mg and the therapeutically effective amount of the Attorney Docket: 51771-0003WO1 sKL protein is 2.5 mg; the therapeutically effective amount of the A2M protein is 5 mg and the therapeutically effective amount of the sKL protein is 1 mg; or the therapeutically effective amount of the A2M protein is 1 mg and the therapeutically effective amount of the sKL protein is 0.25 mg. BRIEF DESCRIPTION OF THE DRAWINGS [0051] FIG.1A depicts an exemplary amino acid sequence of human A2M (GenBank Accession No. NP_000005.2) (SEQ ID NO:1). Lowercase, bold residues are the signal peptide. [0052] FIG.1B depicts an exemplary amino acid sequence of mature human A2M (amino acids 24-1,474 of SEQ ID NO:1) (SEQ ID NO:2). [0053] FIG.1C depicts an exemplary amino acid sequence of human A2M (GenBank Accession No. NP_000005.3) (SEQ ID NO:3). Lowercase residues are the signal peptide. [0054] FIG.1D depicts an exemplary amino acid sequence of mature human A2M (amino acids 24-1,474 of SEQ ID NO:3) (SEQ ID NO:4). [0055] FIG.1E depicts an exemplary amino acid sequence of human A2M (GenBank Accession No. AAA51551.1) (SEQ ID NO:5). Lowercase, bold residues are the signal peptide. [0056] FIG.1F depicts an exemplary amino acid sequence of mature human A2M (amino acids 24-1,474 of SEQ ID NO:5) (SEQ ID NO:6). [0057] FIG.2A-FIG.2B depict an exemplary mRNA sequence encoding human A2M (GenBank Accession No. NM_000014.6) (SEQ ID NO:7). [0058] FIG.3A-FIG.3G depict an alignment of exemplary mouse (SEQ ID NO:8), rat (SEQ ID NO:9), cow (SEQ ID NO:10), macaque (SEQ ID NO:11), human (SEQ ID NO:1), and orangutan (SEQ ID NO:12) A2M proteins. [0059] FIG.3H depicts the percent identity matrix for the alignment of FIG.3A-FIG.3G. [0060] FIG.4A depicts an exemplary amino acid sequence of human klotho (GenBank Accession No. NP_004786.2) (SEQ ID NO:13). Lowercase, bold residues are the signal peptide; lowercase italicized residues are the transmembrane and cytoplasmic domains. Attorney Docket: 51771-0003WO1 [0061] FIG.4B depicts an exemplary amino acid sequence of mature human Klotho (amino acids 34-1,012 of SEQ ID NO:13) (SEQ ID NO:14). [0062] FIG.4C depicts an exemplary amino acid sequence of human soluble Klotho (amino acids 34-981 of SEQ ID NO:13) (SEQ ID NO:15). [0063] FIG.5A-FIG.5B depict an exemplary mRNA sequence encoding human Klotho (GenBank Accession No. NM_004795.4) (SEQ ID NO:16). [0064] FIG.6A-FIG.6E depict an alignment of exemplary mouse (SEQ ID NO:17), rat (SEQ ID NO:18), cow (SEQ ID NO:19), human (SEQ ID NO:14), and macaque (SEQ ID NO:20) Klotho proteins. [0065] FIG.6F depicts the percent identity matrix for the alignment of FIG.6A-FIG.6E. [0066] FIG.7 depicts a graph of IL-6 concentration in PBMCs from Donor 1 at four hours post treatment with the indicated agents. For FIGs.7-16: Virus-No Tx = infected, no treatment; IBZ- 2 = 2µm A2M+0.5µM sKL; IBZ-1 = 1µM A2M+0.25µM sKL; IBZ-0.5 = 0.5µM A2M+0.125µM sKL; A2M-2 = 2µM A2M; A2M-1 = 1µM A2M; A2M-0.5 = 5µM A2M 0.; = sKL-0.5 = 5µM sKL 0.; sKL-0.25 = 25µM sKL 0.; sKL-0.125 = 125µM sKL 0.; WM-1 = 1µm Wortmannin. [0067] FIG.8 depicts a graph of IL-6 concentration in PBMCs from Donor 2 at four hours post treatment with the indicated agents. [0068] FIG.9 depicts a graph of IL-6 concentration in PBMCs from Donor 1 at 24 hours post treatment with the indicated agents. [0069] FIG.10 depicts a graph of IL-6 concentration in PBMCs from Donor 2 at 24 hours post treatment with the indicated agents. [0070] FIG.11 depicts a graph of TNF-alpha concentration in PBMCs from Donor 1 at four hours post treatment with the indicated agents. [0071] FIG.12 depicts a graph of TNF-alpha concentration in PBMCs from Donor 2 at four hours post treatment with the indicated agents. [0072] FIG.13 depicts a graph of TNF-alpha concentration in PBMCs from Donor 1 at 24 hours post treatment with the indicated agents. Attorney Docket: 51771-0003WO1 [0073] FIG.14 depicts a graph of TNF-alpha concentration in PBMCs from Donor 2 at 24 hours post treatment with the indicated agents. [0074] FIG.15 depicts a graph of percent cell viability for MTT assay on PBMCs from Donor 1 at 24 hours post treatment with the indicated agents. [0075] FIG.16 depicts a graph of percent cell viability for MTT assay on PBMCs from Donor 2 at 24 hours post treatment with the indicated agents. [0076] FIG.17 is a series of graphs depicting the concentration of TNF, IL-6, IL-10, IL-8, IL- 1β, IL-12p70, IL-4, IFN-γ, MCP-1, and CCL5 in monocytes isolated from a first healthy donor, treated with the indicated proteins (sKL, A2M, and/or LRPAP) and treated with LPS for 6 hours. [0077] FIG.18 is a series of graphs depicting the concentration of TNF, IL-6, IL-10, IL-8, IL- 1β, IL-12p70, IL-4, IFN-γ, MCP-1, and CCL5 in the monocytes of FIG.17 after treatment with LPS for 24 hours. [0078] FIG.19 is a series of graphs depicting the concentration of TNF, IL-6, IL-10, IL-8, IL- 1β, IL-12p70, IL-4, IFN-γ, MCP-1, and CCL5 in the monocytes of FIG.17 after treatment with LPS for 48 hours. [0079] FIG.20 is a series of graphs depicting the concentration of TNF, IL-6, IL-10, IL-8, IL- 1β, IL-12p70, IL-4, IFN-γ, MCP-1, and CCL5 in monocytes isolated from a second healthy donor, treated with the indicated proteins (sKL, A2M, and/or LRPAP) and treated with LPS for 6 hours. [0080] FIG.21 is a series of graphs depicting the concentration of TNF, IL-6, IL-10, IL-8, IL- 1β, IL-12p70, IL-4, IFN-γ, MCP-1, and CCL5 in the monocytes of FIG.20 after treatment with LPS for 24 hours. [0081] FIG.22 is a series of graphs depicting the concentration of TNF, IL-6, IL-10, IL-8, IL- 1β, IL-12p70, IL-4, IFN-γ, MCP-1, and CCL5 in the monocytes of FIG.20 after treatment with LPS for 48 hours. [0082] FIG.23 is a series of graphs depicting the concentration of TNF, IL-6, IL-10, IL-8, IL- 1β, IL-12p70, IL-4, IFN-γ, MCP-1, and CCL5 in monocytes isolated from a third healthy donor, treated with the indicated proteins (sKL, A2M, and/or LRPAP) and treated with LPS for 6 hours. Attorney Docket: 51771-0003WO1 [0083] FIG.24 is a series of graphs depicting the concentration of TNF, IL-6, IL-10, IL-8, IL- 1β, IL-12p70, IL-4, IFN-γ, MCP-1, and CCL5 in the monocytes of FIG.23 after treatment with LPS for 24 hours. [0084] FIG.25 is a series of graphs depicting the concentration of TNF, IL-6, IL-10, IL-8, IL- 1β, IL-12p70, IL-4, IFN-γ, MCP-1, and CCL5 in the monocytes of FIG.23 after treatment with LPS for 48 hours. [0085] FIG.26 is a series of graphs showing inhibition of NLRP3-mediated IL-1beta in human macrophages treated with the indicated agents at the indicated doses. Error bars reflect the mean with SEM. [0086] FIG.27 is a graph showing the effect of SKL or A2M (or MCC950 control) on NLRP3- mediated IL-1beta release in human macrophages. Error bars reflect the mean with SEM. All groups were compared to vehicle. Statistical analysis using One-Way ANOVA is reflected, with significance of * p≤0.05, **p≤0.01 and *** p≤0.001. P value generated by Kruskall-Wallis test on this result is 0.0006. [0087] FIG.28 is a series of graphs showing percent inhibition of NLRP3-mediated IL-beta production in macrophages treated with the indicated agents at the indicated doses. Error bars reflect the mean with SEM. [0088] FIG.29 is a graph showing the effect of SKL and A2M (or MCC950 control) on IL- 1beta release in human macrophages. Error bars reflect the mean with SEM. All groups were compared to vehicle. Error bars reflect the mean with SEM. All groups were compared to vehicle. Statistical analysis using One-Way ANOVA is reflected, with significance of * p≤0.05, **p≤0.01 and *** p≤0.001. P value generated by Kruskall-Wallis test on this result is 0.0013. [0089] FIG.30 is a graph depicting the percent survival at the indicated hours after the first LPS injection. Group 1 = LPS and saline; Group 2 = LPS, A2M, and sKL. [0090] FIG 31A-FIG.31M is a series of graphs depicting the concentration of the indicated cytokine for the mice of FIG.30. [0091] FIG.32 is a graph depicting the effect of A2M and sKL on SARS-CoV-2 replication in VERO E6 cells. Student t test: p<0.001 relative to infection without active compound (***) or to "RMD[6]" Remdesivir positive control (§§§). Attorney Docket: 51771-0003WO1 [0092] FIG.33 is a series of graphs depicting the effect of A2M on SARS-CoV-2 replication in Calu-3 cells. Results are presented in histogram form (left) with a limit of detection fixed at 1 log10 gene E copy numbers and statistical analysis (*: p<0.001; Student t-test relative to infection without active compound) and in curve form (right) for calculation of inhibitory concentrations. IC50 and IC90 were calculated from SARS-CoV-2 gene E copy values by using a four-parameter logistic regression model. [0093] FIG.34 is a graph depicting the infection rate of Calu-3 cells infected by SARS-CoV-2 treated with A2M, based on NP signal via immunofluorescence. [0094] FIG.35 depicts a series of graphs of SARS-CoV-2 alpha (A, B, C) or delta (D, E, F) virus RNA in infected cells treated with A2M and sKL (A and D), A2M (B and E), or sKL (C and F) at varying concentrations. MOI = 0.05. A2M tested at 2 µM, 1 µM, 0.5 µM, and 0.25 µM. sKL tested at 0.5 µM, 0.25 µM, 0.125 µM, and 0.06 µM. IBZ-01=combination of A2M and sKL. IBZ-01 tested at A2M:sKL concentrations of 2µM:0.5µM; 1µM:0.25µM; 0.5µM:0.125µM; and 0.25µM:0.06µM. [0095] FIG.36 depicts a series of graphs of SARS-CoV-2 alpha (A, B) or delta (C, D) virus RNA in infected cells treated with A2M and/or sKL or Remdesivir. MOI = 0.001. IBZ-01 (1+0.25) =1 µM A2M+0.25 µM sKL); A2M-1=A2m 1µM; sKL-02=sKL 0.5 µM; RDV- 5=Remdesivir 5 µM; Virus-No Tx = virus, no treatment. [0096] FIG.37 is a graph depicting SARS-CoV-2 alpha virus RNA copies/mL at 24 hours after infection in infected cells treated with A2M and sKL (IBZ), A2M, or sKL at varying concentrations. For FIGs.37-40: IBZ-2 = 2 µM A2M+0.5 µM sKL; IBZ-1 = 1 µM A2M+0.25 µM sKL; IBZ-0.5 = 0.5 µM A2M+0.125 µM sKL; A2M-2 = 2 µM A2M; A2M-1 = 1 µM A2M; A2M-0.5 = 0.5 µM A2M; sKl-0.5 = 0.5 µM sKL; sKl-0.25 = 0.25 µM sKL; sKl-0.125 = 0.125 µM sKL; RDV-2 = 2 µM Remdesivir. [0097] FIG.38 is a graph depicting SARS-CoV-2 alpha virus RNA copies/mL at 48 hours after infection in infected cells treated with A2M and sKL (IBZ), A2M, or sKL at varying concentrations. Attorney Docket: 51771-0003WO1 [0098] FIG.39 is a graph depicting SARS-CoV-2 delta virus RNA copies/mL at 24 hours after infection in infected cells treated with A2M and sKL (IBZ), A2M, or sKL at varying concentrations. [0099] FIG.40 is a graph depicting SARS-CoV-2 delta virus RNA copies/mL at 48 hours after infection in infected cells treated with A2M and sKL (IBZ), A2M, or sKL at varying concentrations. [00100] FIG.41 is a series of graphs depicting the percent inhibition of catalytic activity of SARS-CoV-2 PLpro in the presence of varying concentrations of PR619, A2M, sKL, or A2M and sKL. [00101] FIG.42 is a series of graphs depicting the percent inhibition of catalytic activity of SARS-CoV-2 PLpro in the presence of varying concentrations of PR619, A2M, sKL, or A2M and sKL. [00102] FIG.43 is a series of graphs depicting the percent inhibition of binding of the SARS-CoV-2 spike receptor binding domain (RBD) to angiotensin-converting enzyme 2 (ACE2) in the presence of varying concentrations of buffer alone (ACE2-His), A2M, sKL, or A2M and sKL. [00103] FIG.44 is a series of graphs depicting the percent inhibition of binding of the SARS-CoV-2 spike RBD to ACE2 in the presence of varying concentrations of buffer alone (ACE2-His), A2M, sKL, or A2M and sKL. [00104] FIG.45 is a series of graphs depicting the percent inhibition of cathepsin L activity in the presence of A2M and/or sKL or E64. [00105] FIG.46 is a series of graphs depicting the percent inhibition of 3CL Mpro activity upon treatment with BTB0-7418 (control), sKL, A2M, or A2M and sKL at the indicated doses. [00106] FIG.47 is a graph depicting the infection rate normalized over the non-treated condition. Concentrations are in µM. [00107] FIG.48 is a graph depicting the replication rate normalized over the non-treated condition. Concentrations are in µM. Attorney Docket: 51771-0003WO1 [00108] FIG.49 is a graph depicting the infection rate normalized over the non-treated condition. Concentrations are in µM. [00109] FIG.50 is a graph depicting the replication rate normalized over the non-treated condition. Concentrations are in µM. [00110] FIG.51 is a graph depicting serum IL-1 beta levels for the indicated treatment groups (from left to right: Group 1-Group 5, respectively). [00111] FIG.52 is a graph depicting serum IL-1 beta levels for the indicated treatment groups, relative to group 2 (from left to right: Group 1-Group 5, respectively). [00112] FIG.53 is a graph depicting serum IL-6 levels for the indicated treatment groups (from left to right: Group 1-Group 5, respectively). [00113] FIG.54 is a graph depicting serum IL-10 levels for the indicated treatment groups (from left to right: Group 1-Group 5, respectively). [00114] FIG.55 is a graph depicting serum TNF-alpha levels for the indicated treatment groups (from left to right: Group 1-Group 5, respectively). [00115] FIG.56 is a graph depicting BALF cell counts for the indicated treatment groups (for each cell type, from left to right: Group 1-Group 5, respectively). [00116] FIG.57 is a graph depicting BALF cell percentages for the indicated treatment groups (for each cell type, from left to right: Group 1-Group 5, respectively). [00117] FIG.58 is a graph depicting the number of cells (Y-axis), normalized over the non-treated, infected condition, and treated with the indicated compounds. [00118] FIG.59 is a graph depicting the infection rate (Y-axis), normalized over the non- treated, infected condition, for the experiment of FIG.58. [00119] FIG.60 is a graph depicting the replication rate (Y-axis), normalized over the non-treated condition for the experiment of FIG.58. [00120] FIG.61 is a graph depicting the replication rate (Y-axis), normalized over the non-treated condition for the experiment, corrected by the number of infected cells of FIG.58. Attorney Docket: 51771-0003WO1 [00121] FIG.62 is a graph depicting the proteasome 20s activity (Y-axis), normalized over the non-treated, non-infected condition, for the experiment of FIG.58. DETAILED DESCRIPTION OF THE INVENTION [00122] This disclosure is based, in part, on the surprising finding that A2M and sKL synergize with each other, despite not directly binding to each other. In particular, the working examples herein demonstrate that A2M and sKL exhibit an enhanced antiviral effect against SARS-CoV-2. A2M and sKL, alone and in combination, also reduce the inflammatory response in model of inflammation and bacterial infection. The working examples also demonstrate that A2M and sKL inhibit cathepsin L and the interaction between the SARS-CoV-2 spike protein and its receptor, ACE2, and synergize to inhibit SARS-CoV-2 PLpro. [00123] Thus, provided herein are A2M proteins and sKL proteins and compositions comprising the same and related methods of making same, polynucleotides, vectors, and cells. This disclosure also provides compositions (e.g., pharmaceutical compositions) comprising both an A2M protein and an sKL protein. Also provided herein are methods of treating a coronavirus (e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, treating post- acute sequelae (PASC), treating inflammation, treating bacterial infection, inhibiting an interaction between a SARS-CoV-2 spike protein and an angiotensin-converting enzyme 2 (ACE2) protein, inhibiting a coronavirus (e.g., SARS-CoV-2) papain-like protease (PLpro) protein, rejuvenating skin, and cosmetically treating skin, involving administering A2M and/or sKL. A2M [00124] The present disclosure provides an A2M protein, compositions comprising an A2M protein, and methods of use thereof. In some instances, the compositions comprising an A2M protein further comprise an sKL protein. In some instances, the A2M protein (or compositions comprising the A2M protein) are for use in combination with an sKL protein (or a Attorney Docket: 51771-0003WO1 composition comprising an sKL protein). Also provided herein are methods of making an A2M protein, including related polynucleotides, vectors, and cells. [00125] A2M (also known in the art as C3 and PZP-like alpha-2-macroglobulin domain- containing protein 5 (CPAMD5)) is a 1,474-amino acid (including the 23-amino acid signal peptide) protein that functions as a broad-spectrum protease-binding protein. Human A2M is a 720 kDa homotetramer comprised of four 180 kDa subunits. The subunits are paired by disulfide bonds to form covalently-linked dimers, which non-covalently associate to form the cage-like quaternary structure of A2M. [00126] Exemplary amino acid sequences of full-length human A2M are provided in SEQ ID NOs:1, 3, and 5 (FIG.1A, FIG.1C, FIG.1E). Exemplary amino acid sequences of full- length mature human A2M are provided in SEQ ID NOs:2, 4, and 6 (FIG.1B, FIG.1D, FIG. 1F). An exemplary nucleic acid sequence of an mRNA encoding human A2M is provided in SEQ ID NO:7 (FIG.2A-FIG.2B). [00127] A2M proteins among different species have high homology. See FIG.3A-FIG. 3G for an alignment of exemplary amino acid sequences for A2M proteins from human, mouse, rat, macaque, orangutan, and bovine. In some instances, the A2M protein is a human A2M protein (e.g., SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6). The skilled artisan will understand that region(s) or amino acid(s) amenable to variation (e.g., substitution, insertion, or deletion) may be identified by comparing a reference A2M sequence to a homolog or known variant and determining region(s) or amino acid(s) that are not conserved (see, e.g., FIG.3A-FIG.3G or compare SEQ ID NOs:2, 4, and 6). [00128] In certain instances, the A2M protein comprises a modified amino acid sequence of a wild type A2M protein (e.g., a modified amino acid sequence of wild type human A2M protein, e.g., SEQ ID NO:2). In certain instances, the A2M protein described herein binds trypsin. [00129] In certain instances, the A2M protein described herein may contain one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) amino acid substitutions (relative to SEQ ID NO:2, SEQ ID NO:4, or SEQ ID NO:6), e.g., one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) conservative and/or non-conservative amino acid substitutions. In certain instances, these substitution(s) are of amino acids that directly Attorney Docket: 51771-0003WO1 interact with an A2M protein binding partner known in the art or described herein (e.g., FGF1, FGF2, FGF-4, FGF-6, IFN-gamma, IL-1beta, IL2, IL-4, IL-6, IL-8, IL-18, NGF-beta, PDGF, TGF-beta1, TGF-beta2, TNF-alpha, VEGF). In certain instances, these substitution(s) are of amino acids that do not directly interact with an A2M protein binding partner known in the art or described herein (e.g., FGF1, FGF2, FGF-4, FGF-6, IFN-gamma, IL-1beta, IL2, IL-4, IL-6, IL-8, IL-18, NGF-beta, PDGF, TGF-beta1, TGF-beta2, TNF-alpha, VEGF). In certain instances, these substitutions are of both amino acids that directly interact with an A2M protein binding partner known in the art or described herein and amino acids that do not directly interact with an A2M protein binding partner known in the art or described herein. In some instances, the A2M protein comprises an aspartic acid (D) at the amino acid corresponding to position 616 of SEQ ID NO:2. In some instances, the A2M protein comprises a valine (V) at the amino acid corresponding to position 977 of the amino acid sequence set forth in SEQ ID NO:2. In some instances, the A2M protein comprises an aspartic acid (D) at the amino acid corresponding to position 616 of SEQ ID NO:2 and a valine (V) at the amino acid corresponding to position 977 of the amino acid sequence set forth in SEQ ID NO:2. In certain instances, the A2M protein described herein binds trypsin. [00130] In some instances, the substitutions are conservative amino acid substitutions. In some instances, the substitutions are non-conservative amino acid substitutions. In some instances, the substitutions are with conservative amino acid substitutions and non-conservative amino acid substitutions. A “conservative amino acid substitution” means that the substitution replaces one amino acid with another amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine), aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine), and acidic side chains and their amides (e.g., aspartic acid, glutamic acid, asparagine, glutamine). Attorney Docket: 51771-0003WO1 [00131] In certain instances, the A2M protein described herein has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or 100% sequence identity to an A2M protein sequence known in the art or described herein (e.g., SEQ ID NO:2, SEQ ID NO:4, or SEQ ID NO:6). In certain instances, the A2M protein described herein binds trypsin. The variability in the amino acid sequence may be in region(s) that directly interact with an A2M protein binding partner known in the art or described herein and/or in region(s) that do not directly interact with an A2M protein binding partner known in the art or described herein. Methods for determining percent identity between sequences are known in the art. For example, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). In a preferred instance, the length of a reference sequence aligned for comparison purposes is at least 30%, preferably at least 40%, more preferably at least 50%, even more preferably at least 60%, and even more preferably at least 70%, 80%, 90%, or 100% of the length of the reference sequence. The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The determination of percent identity between two amino acid sequences is accomplished using the BLAST 2.0 program. Sequence comparison is performed using an ungapped alignment and using the default parameters (Blossom 62 matrix, gap existence cost of 11, per residue gapped cost of 1, and a lambda ratio of 0.85). The mathematical algorithm used in BLAST programs is described in Altschul et al. (Nucleic Acids Res.25:3389-3402, 1997). [00132] In certain instances, the A2M protein described herein may also contain one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) deletions from the N- and/or C-terminus of the A2M protein. In certain instances, the A2M protein is 1,000-1,474, 1,000-1,400, 1,000-1,300, 1,000-1,200, 1,200-1,500, 1,300-1,500, or 1,400-1,500 amino acids in length. In certain instances, the A2M protein is 1,451 amino acids in length. In certain instances, the A2M protein described herein binds trypsin. Attorney Docket: 51771-0003WO1 [00133] In certain instances, the A2M protein described herein comprises the amino acid sequence of SEQ ID NO:2. In certain instances, the A2M protein described herein consists of the amino acid sequence of SEQ ID NO:2. In certain instances, the A2M protein is part of a composition (e.g., a pharmaceutical composition). In certain instances, the A2M protein is part of a composition (e.g., a pharmaceutical composition) further comprising an sKL protein (e.g., an sKL protein described herein). In certain instances, the A2M protein (or a composition comprising the A2M protein) is for use in combination with an sKL protein (or a composition, e.g., a pharmaceutical composition, comprising an sKL protein, e.g., an sKL protein described herein). In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. [00134] In certain instances, the A2M protein described herein comprises the amino acid sequence of SEQ ID NO:4. In certain instances, the A2M protein described herein consists of the amino acid sequence of SEQ ID NO:4. In certain instances, the A2M protein is part of a composition (e.g., a pharmaceutical composition). In certain instances, the A2M protein is part of a composition (e.g., a pharmaceutical composition) further comprising an sKL protein (e.g., an sKL protein described herein). In certain instances, the A2M protein (or a composition comprising the A2M protein) is for use in combination with an sKL protein (or a composition, e.g., a pharmaceutical composition, comprising an sKL protein, e.g., an sKL protein described herein). In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. [00135] In certain instances, the A2M protein described herein comprises the amino acid sequence of SEQ ID NO:6. In certain instances, the A2M protein described herein consists of the amino acid sequence of SEQ ID NO:6. In certain instances, the A2M protein is part of a composition (e.g., a pharmaceutical composition). In certain instances, the A2M protein is part of a composition (e.g., a pharmaceutical composition) further comprising an sKL protein (e.g., an sKL protein described herein). In certain instances, the A2M protein (or a composition comprising the A2M protein) is for use in combination with an sKL protein (or a composition, e.g., a pharmaceutical composition, comprising an sKL protein, e.g., an sKL protein described Attorney Docket: 51771-0003WO1 herein). In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. [00136] In some instances, the A2M protein described herein is in monomeric form, dimeric form, or tetrameric form. In some instances, the A2M protein described herein is in tetrameric form. In some instances, the A2M protein described herein is in dimeric form. Methods of determining A2M protein is in monomeric, dimeric, or tetrameric form are known in the art, such as, e.g., polyacrylamide gel electrophoresis. Methods of obtaining A2M protein in monomeric, dimeric, or tetrameric form are known in the art, such as, e.g., exposure of tetrameric A2M to an oxidant (e.g., hypochlorite) to produce dimeric A2M. [00137] In certain instances, the A2M protein inhibits cathepsin L activity (e.g., reduces cathepsin L activity by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at lease 90%, or 100% compared to cathepsin L activity in the absence of the A2M protein). Methods of determining whether A2M protein inhibits cathepsin L activity are known in the art (see, e.g., the Examples described herein). [00138] In certain instances, the A2M protein inhibits binding between ACE2 and SARS- CoV-2 S protein (e.g., reduces binding between ACE2 and SARS-CoV-2 S protein by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at lease 90%, or 100% compared to cathepsin L activity in the absence of the A2M protein). Methods of determining whether A2M protein inhibits binding between ACE2 and SARS-CoV-2 S protein (see, e.g., the Examples described herein). [00139] In certain instances, the A2M protein described herein binds trypsin. Methods of determining whether an A2M protein binds trypsin are known in the art, e.g., co-localization assays, co-immunoprecipitation assays, ELISA, Biacore, SPR, the trypsin binding assay described in Wyatt et al., 2015, PLOS ONE, DOI:10.1371/journal.pone.0130036, which is incorporated by reference herein in its entirety, and Trypsin Activity Colorimetric Assay Kit (AssayGenie, Catalog #BN00984). [00140] In certain instances, the A2M protein described herein binds FGF23. Methods of determining whether an A2M protein binds FGF23 are known in the art, e.g., co-localization assays, co-immunoprecipitation assays, ELISA, Biacore, and SPR. Attorney Docket: 51771-0003WO1 [00141] In certain instances, the A2M protein described herein binds FGF2. Methods of determining whether an A2M protein binds FGF2 are known in the art, e.g., co-localization assays, co-immunoprecipitation assays, ELISA, Biacore, and SPR. sKL [00142] The present disclosure provides an sKL protein, compositions comprising an sKL protein, and methods of use thereof. In some instances, the compositions comprising an sKL protein further comprise an A2M protein (e.g., as described herein). In some instances, the sKL protein (or compositions comprising the sKL protein) are for use in combination with an A2M protein (or a composition comprising an A2M protein). Also provided herein are methods of making an sKL protein, including related polynucleotides, vectors, and cells. [00143] KL is a 1,012-amino acid protein (including the 33 amino acid signal peptide) that is a member of the glycosidase-1 superfamily and hydrolyzes steroid β-glucuronides. KL may act as a co-receptor for FGF23. KL exists in two main forms: full-length, membrane-bound KL (e.g., SEQ ID NO:14) and sKL (e.g., SEQ ID NO:15). sKL is formed from proteolytic cleavage of membrane-bound KL. sKL does not include the cytoplasmic domain (e.g., amino acids 1,003- 1,012 of SEQ ID NO:13) nor the transmembrane domain (e.g., amino acids 982-1,002 of SEQ ID NO:13). [00144] An exemplary amino acid sequence of full-length human KL is provided in SEQ ID NO:13 (FIG.4A). An exemplary amino acid sequence of full-length mature human KL is provided in SEQ ID NO:14 (FIG.4B). An exemplary amino acid sequence of full-length mature human sKL is provided in SEQ ID NO:15 (FIG.4C). An exemplary nucleic acid sequence of an mRNA encoding human KL is provided in SEQ ID NO:16 (FIG.5A-FIG.5B). [00145] KL proteins among different species have high homology. See FIG.6A-FIG.6F for an alignment of exemplary amino acid sequences for KL proteins from mouse, rat, cow, human, and macaque. In some instances, the sKL protein is a human sKL protein (e.g., SEQ ID NO:15). The skilled artisan will understand that region(s) or amino acid(s) amenable to variation (e.g., substitution, insertion, or deletion) may be identified by comparing a reference KL Attorney Docket: 51771-0003WO1 sequence to a homolog and determining region(s) or amino acid(s) that are not conserved (see, e.g., FIG.6A-FIG.6F). [00146] In certain instances, the sKL protein comprises a modified amino acid sequence of a wild type sKL protein (e.g., a modified amino acid sequence of wild type human sKL protein, e.g., the amino acid sequence set forth in SEQ ID NO:15). [00147] In certain instances, the sKL protein comprises a valine (V) at the amino acid corresponding to position 12 of SEQ ID NO:15. [00148] In certain instances, the sKL protein comprises a phenylalanine (F) at the amino acid corresponding to position 12 of SEQ ID NO:15. [00149] In some instances, the sKL protein comprises the amino acids corresponding to positions 34-503 of SEQ ID NO:13. In some instances, the sKL protein comprises the amino acids corresponding to positions 515-956 of SEQ ID NO:13. In some instances, the sKL protein comprises the amino acids corresponding to positions 34-503 of SEQ ID NO:13 and the amino acids corresponding to positions 515-956 of SEQ ID NO:13. In some instances, the sKL protein comprises the amino acids corresponding to positions 504-515 of SEQ ID NO:13. In some instances, the sKL protein comprises the amino acids corresponding to positions 967-981 of SEQ ID NO: 13. In some instances, the sKL protein comprises the amino acids corresponding to positions 957-981 of SEQ ID NO: 13. In some instances, the sKL protein does not comprise the amino acids corresponding to positions 967-981 of SEQ ID NO:13. In some instances, the sKL comprises the amino acids corresponding to positions 34-981 of SEQ ID NO:13. In some instances, the sKL comprises the amino acids corresponding to positions 34-966 of SEQ ID NO:13. In some instances, the C-terminus of the sKL protein corresponds to position 966 of SEQ ID NO:13. In some instances, the C-terminus of the sKL protein corresponds to position 981 of SEQ ID NO:13. [00150] In certain instances, the sKL protein described herein may contain one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) amino acid substitutions (relative to a wild type sKL protein sequence (e.g., SEQ ID NO:15)), e.g., one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) conservative and/or non-conservative amino acid substitutions. In certain instances, these substitution(s) are of amino acids that directly interact with an sKL protein binding partner known in the art or described herein (e.g., Attorney Docket: 51771-0003WO1 FGF23). In certain instances, these substitution(s) are of amino acids that do not directly interact with an sKL protein binding partner known in the art or described herein (e.g., FGF23). In certain instances, these substitutions are of both amino acids that directly interact with an sKL protein binding partner known in the art or described herein and amino acids that do not directly interact with an sKL protein binding partner known in the art or described herein. [00151] In some instances, the substitutions are conservative amino acid substitutions. In some instances, the substitutions are non-conservative amino acid substitutions. In some instances, the substitutions are with conservative amino acid substitutions and non-conservative amino acid substitutions. [00152] In certain instances, the sKL protein described herein has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 97% or 100% sequence identity to an sKL protein sequence known in the art or described herein (e.g., SEQ ID NO:15). The variability in the amino acid sequence may be in region(s) that directly interact with an sKL protein binding partner known in the art or described herein and/or in region(s) that do not directly interact with an sKL protein binding partner known in the art or described herein. [00153] In certain instances, the sKL protein described herein may also contain one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) deletions from the N- and/or C-terminus of the sKL protein. In certain instances, the sKL protein is 750-1200, 750- 1100, 750-1000, 850-1200, 840-1100, 850-1000, or 900-1000 amino acids in length. In certain instances, the sKL protein is 948 amino acids in length. In some instances, the sKL is 948 amino acids in length, the N-terminus of the sKL protein corresponds to position 34 of SEQ ID NO;13, and the C-terminus of the sKL protein corresponds to position 981 of SEQ ID NO:13. [00154] In certain instances, the sKL protein described herein comprises the amino acid sequence of SEQ ID NO:15. In certain instances, the sKL protein described herein consists of the amino acid sequence of SEQ ID NO:15. In certain instances, the sKL protein is part of a composition (e.g., a pharmaceutical composition). In certain instances, the sKL protein is part of a composition (e.g., a pharmaceutical composition) further comprising an A2M protein (e.g., an A2M protein described herein). In certain instances, the sKL protein (or a composition comprising the sKL protein) is for use in combination with an A2M protein (or a composition, Attorney Docket: 51771-0003WO1 e.g., a pharmaceutical composition, comprising an A2M protein, e.g., an A2M protein described herein). In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. [00155] In certain instances, the sKL protein described herein binds FGF23. Methods of determining whether an sKL protein binds FGF23 are known in the art, e.g., co-localization assays, co-immunoprecipitation assays, ELISA, Biacore, and SPR. [00156] In certain instances, the sKL protein described herein induces ERK1/2 phosphorylation (e.g., in a cell assay). Methods of determining whether an sKL protein induces ERK1/2 phosphorylation (e.g., in a cell assay) are known in the art, e.g., western blot, ELISA, immunofluorescence. See, e.g., Zhong et al., 2020, JBC, 295(10:3115-3133, which is incorporated by reference herein in its entirety, for a description of an exemplary ERK1/2 phosphorylation assay. [00157] In certain instances, the sKL protein described herein induces ERK1/2 phosphorylation (e.g., in a cell assay). Methods of determining whether an sKL protein induces ERK1/2 phosphorylation (e.g., in a cell assay) are known in the art, e.g., western blot, ELISA, immunofluorescence. See, e.g., Zhong et al., 2020, JBC, 295(10:3115-3133, which is incorporated by reference herein in its entirety, for a description of an exemplary ERK1/2 phosphorylation assay. See, also, the Phospho(Thr202/Tyr204; Thr184/Tyr187)/Total ERK1/2 Assay (Mesoscale, Catalog No. K15107D-1). PHARMACEUTICAL COMPOSITIONS [00158] The A2M protein described herein can be formulated for use as or in a pharmaceutical composition. Similarly, the sKL protein described herein can be formulated for use as or in a pharmaceutical composition. Similarly, the A2M protein described herein and the sKL protein described herein can be formulated for use as or in a pharmaceutical composition. Attorney Docket: 51771-0003WO1 The pharmaceutical compositions may be used in the methods of treatment or prevention described herein. [00159] Thus, provided herein is a pharmaceutical composition comprising an A2M protein (e.g., in a therapeutically effective amount) and a pharmaceutically acceptable carrier. [00160] Also provided herein is a pharmaceutical composition comprising an sKL protein (e.g., in a therapeutically effective amount) and a pharmaceutically acceptable carrier. [00161] Also provided herein is a pharmaceutical composition comprising an A2M protein (e.g., in a therapeutically effective amount), an sKL protein (e.g., in a therapeutically effective amount), and a pharmaceutically acceptable carrier. In some instances, the A2M protein and the sKL protein are present in the pharmaceutical composition at an A2M:sKL ratio of about 1:1, about 2:1, about 2.5:1, about 3:1, about 4:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1, about 10:1, about 11:1, about 12:1, about 20:1, about 30:1, about 40:1, about 50:1, about 60:1, about 70:1, about 80:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, or about 1:10. In some instances, the A2M protein and the sKL protein are present in the pharmaceutical composition at a A2M:sKL ratio of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. In some instances, the A2M protein and the sKL protein are present in the pharmaceutical composition at a A2M:sKL ratio of 1:1. In some instances, the A2M protein and the sKL protein are present in the pharmaceutical composition at a A2M:sKL ratio of 2.5:1. In some instances, the A2M protein and the sKL protein are present in the pharmaceutical composition at a A2M:sKL ratio of 5:1. In some instances, the A2M protein and the sKL protein are present in the pharmaceutical composition at a A2M:sKL ratio of 10:1. In some instances, the A2M protein and the sKL protein are present in the pharmaceutical composition at a A2M:sKL ratio of 11:1. In some instances, the A2M protein and the sKL protein are present in the pharmaceutical composition at a A2M:sKL ratio of 12:1. In some instances, the A2M protein and the sKL protein are present in the pharmaceutical composition at a A2M:sKL ratio of 50:1. The term “about” in the context of an A2M:sKL ratio means +/-10% of the recited value. [00162] Such pharmaceutical compositions can be formulated or adapted for administration to a subject via any route, e.g., any route approved by the Food and Drug Administration (FDA). Exemplary methods are described in the FDA’s CDER Data Standards Manual, version number 004 (which is available at fda.give/cder/dsm/DRG/drg00301.htm). For Attorney Docket: 51771-0003WO1 example, compositions can be formulated or adapted for administration by inhalation (e.g., oral and/or nasal inhalation (e.g., via nebulizer or spray)), injection (e.g., parental, intravenously, intra-arterial, subdermally, intraperitoneally, intramuscularly, microneedling, and/or subcutaneously); and/or for oral administration, transmucosal administration, and/or topical administration (including topical (e.g., nasal) sprays, rub-on, patches, and/or solutions). The term “parenteral” as used herein includes subcutaneous, intra-cutaneous, intra-venous, intra- muscular, intra-articular, intra-arterial, intra-synovial, intra-sternal, intra-thecal, intra-lesional and intra-cranial injection or infusion techniques. The pharmaceutical compositions may be sterile. [00163] In some instances, the pharmaceutical compositions are formulated for subcutaneous administration to a subject (e.g., human). [00164] In some instances, the pharmaceutical compositions are formulated for topical administration to a subject (e.g., human). [00165] In certain instances, the pharmaceutical composition comprises an A2M protein described herein and a pharmaceutically acceptable carrier. In some instances, the pharmaceutical composition comprises an A2M protein that is identical to the amino acid sequence of SEQ ID NO:2 except for 1 to 50, 1 to 40, 1 to 30, 1 to 20, 1 to 10, 1 to 5, 1 to 3, 2, or 1 amino acid substitutions, insertions, or deletions. These changes to the amino acid sequence can be made in region(s) that directly interact with an A2M protein binding partner and/or in region(s) that do not directly interact with an A2M protein binding partner. In some instances, the pharmaceutical composition comprises an A2M protein comprising the amino acid sequence of SEQ ID NO:2. In some instances, the pharmaceutical composition comprises an A2M protein consisting of the amino acid sequence of SEQ ID NO:2. In some instances, the pharmaceutical composition comprises A2M protein in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in the pharmaceutical composition is in dimeric form. In some instances, the pharmaceutical composition further comprises an sKL protein described herein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the pharmaceutical composition comprising an A2M protein Attorney Docket: 51771-0003WO1 described herein is for use in combination with a pharmaceutical composition comprising an sKL protein. In some instances, the pharmaceutical composition comprising an A2M protein is formulated for subcutaneous administration to a subject (e.g., human). In some instances, the pharmaceutical composition comprising an A2M protein is formulated for topical administration to a subject (e.g., human). In some instances, a pharmaceutical composition comprising an sKL protein for use in combination with a pharmaceutical composition comprising an A2M protein is formulated for subcutaneous administration to a subject (e.g., human). In some instances, a pharmaceutical composition comprising an sKL protein for use in combination with a pharmaceutical composition comprising an A2M protein is formulated for topical administration to a subject (e.g., human). [00166] In certain instances, the pharmaceutical composition comprises an A2M protein described herein and a pharmaceutically acceptable carrier. In some instances, the pharmaceutical composition comprises an A2M protein that is identical to the amino acid sequence of SEQ ID NO:4 except for 1 to 50, 1 to 40, 1 to 30, 1 to 20, 1 to 10, 1 to 5, 1 to 3, 2, or 1 amino acid substitutions, insertions, or deletions. These changes to the amino acid sequence can be made in region(s) that directly interact with an A2M protein binding partner and/or in region(s) that do not directly interact with an A2M protein binding partner. In some instances, the pharmaceutical composition comprises an A2M protein comprising the amino acid sequence of SEQ ID NO:4. In some instances, the pharmaceutical composition comprises an A2M protein consisting of the amino acid sequence of SEQ ID NO:4. In some instances, the pharmaceutical composition comprises A2M protein in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in the pharmaceutical composition is in dimeric form. In some instances, the pharmaceutical composition further comprises an sKL protein described herein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the pharmaceutical composition comprising an A2M protein described herein is for use in combination with a pharmaceutical composition comprising an sKL protein. In some instances, the pharmaceutical composition comprising an A2M protein is formulated for subcutaneous administration to a subject (e.g., human). In some instances, the pharmaceutical composition comprising an A2M protein is formulated for topical administration Attorney Docket: 51771-0003WO1 to a subject (e.g., human). In some instances, a pharmaceutical composition comprising an sKL protein for use in combination with a pharmaceutical composition comprising an A2M protein is formulated for subcutaneous administration to a subject (e.g., human). In some instances, a pharmaceutical composition comprising an sKL protein for use in combination with a pharmaceutical composition comprising an A2M protein is formulated for topical administration to a subject (e.g., human). [00167] In certain instances, the pharmaceutical composition comprises an A2M protein described herein and a pharmaceutically acceptable carrier. In some instances, the pharmaceutical composition comprises an A2M protein that is identical to the amino acid sequence of SEQ ID NO:6 except for 1 to 50, 1 to 40, 1 to 30, 1 to 20, 1 to 10, 1 to 5, 1 to 3, 2, or 1 amino acid substitutions, insertions, or deletions. These changes to the amino acid sequence can be made in region(s) that directly interact with an A2M protein binding partner and/or in region(s) that do not directly interact with an A2M protein binding partner. In some instances, the pharmaceutical composition comprises an A2M protein comprising the amino acid sequence of SEQ ID NO:6. In some instances, the pharmaceutical composition comprises an A2M protein consisting of the amino acid sequence of SEQ ID NO:6. In some instances, the pharmaceutical composition comprises A2M protein in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in the pharmaceutical composition is in dimeric form. In some instances, the pharmaceutical composition further comprises an sKL protein described herein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the pharmaceutical composition comprising an A2M protein described herein is for use in combination with a pharmaceutical composition comprising an sKL protein. In some instances, the pharmaceutical composition comprising an A2M protein is formulated for subcutaneous administration to a subject (e.g., human). In some instances, the pharmaceutical composition comprising an A2M protein is formulated for topical administration to a subject (e.g., human). In some instances, a pharmaceutical composition comprising an sKL protein for use in combination with a pharmaceutical composition comprising an A2M protein is formulated for subcutaneous administration to a subject (e.g., human). In some instances, a pharmaceutical composition comprising an sKL protein for use in combination with a Attorney Docket: 51771-0003WO1 pharmaceutical composition comprising an A2M protein is formulated for topical administration to a subject (e.g., human). [00168] In certain instances, the pharmaceutical composition comprises an sKL protein described herein and a pharmaceutically acceptable carrier. In some instances, the pharmaceutical composition comprises an sKL protein that is identical to the amino acid sequence of SEQ ID NO:15 except for 1 to 50, 1 to 40, 1 to 30, 1 to 20, 1 to 10, 1 to 5, 1 to 3, 2, or 1 amino acid substitutions, insertions, or deletions. These changes to the amino acid sequence can be made in region(s) that directly interact with an sKL protein binding partner and/or in region(s) that do not directly interact with an sKL protein binding partner. In some instances, the pharmaceutical composition comprises an sKL protein comprising the amino acid sequence of SEQ ID NO:15. In some instances, the pharmaceutical composition comprises an sKL protein consisting of the amino acid sequence of SEQ ID NO:15. In some instances, the pharmaceutical composition further comprises an A2M protein described herein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the pharmaceutical composition comprising an sKL protein described herein is for use in combination with a pharmaceutical composition comprising an A2M protein. In some instances, the pharmaceutical composition comprising an sKL protein is formulated for subcutaneous administration to a subject (e.g., human). In some instances, the pharmaceutical composition comprising an sKL protein is formulated for topical administration to a subject (e.g., human). In some instances, a pharmaceutical composition comprising an A2M protein for use in combination with a pharmaceutical composition comprising an sKL protein is formulated for subcutaneous administration to a subject (e.g., human). In some instances, a pharmaceutical composition comprising an A2M protein for use in combination with a pharmaceutical composition comprising an sKL protein is formulated for topical administration to a subject (e.g., human). Attorney Docket: 51771-0003WO1 [00169] In some instances, pharmaceutical compositions can include an effective amount of the A2M protein and/or the sKL protein. The terms “effective amount” and “effective to treat,” as used herein, refer to an amount or a concentration of A2M protein and/or sKL protein or a pharmaceutical composition described herein utilized for a period of time (including acute or chronic administration and periodic or continuous administration) that is effective within the context of its administration for causing an intended effect or physiological outcome. [00170] Pharmaceutical compositions described herein can include any pharmaceutically acceptable carrier and/or vehicle. Pharmaceutically acceptable carriers and/or vehicles are known in the art. See, e.g., Remington’s Pharmaceutical Sciences (1990) Mack Publishing Co., Easton, PA. [00171] The term “pharmaceutically acceptable carrier” refers to a carrier that may be administered to a subject (e.g., human), together with an agent of this invention (e.g., an A2M protein and/or an sKL protein), and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the agent. [00172] The pharmaceutical compositions described herein may contain any conventional non-toxic pharmaceutically-acceptable carriers, adjuvants or vehicles. In some cases, the pH of the formulation may be adjusted with pharmaceutically acceptable acids, bases or buffers to enhance the stability of the formulated compound or its delivery form. [00173] In some instances, the pharmaceutical composition comprises about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, or about 10 mg of the A2M protein. In some instances, the pharmaceutical composition comprises about 1 mg to about 10 mg, about 1 mg to about 9 mg, about 1 mg to about 8 mg, about 1 mg to about 7 mg, about 1 mg to about 6 mg, about 1 mg to about 5 mg, about 1 mg to about 4 mg, about 1 mg to about 3 mg, about 1 mg to about 2 mg, about 5 mg to about 10 mg, about 5 mg to about 9 mg, about 5 mg to about 8 mg, about 5 mg to about 7 mg, or about 5 mg to about 6 mg of the A2M protein. In some instances, the pharmaceutical composition comprises about 1 mg of the A2M protein. In some instances, the pharmaceutical composition comprises about 5 mg of the A2M protein. In some instances, the pharmaceutical composition comprises about 10 mg of the A2M protein. In some instances, the pharmaceutical composition comprises 1 mg of the Attorney Docket: 51771-0003WO1 A2M protein. In some instances, the pharmaceutical composition comprises 5 mg of the A2M protein. In some instances, the pharmaceutical composition comprises 10 mg of the A2M protein. In some instances, the pharmaceutical composition comprises about 0.2 mg, about 0.25 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1.0 mg, about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2.0 mg, about 2.25 mg, or about 2.5 mg of the sKL protein. In some instances, the pharmaceutical composition comprises about 0.25 mg to about 2.5 mg, about 0.25 mg to about 2.25 mg, about 0.25 mg to about 2.0 mg, about 0.25 mg to about 1.75 mg, about 0.25 mg to about 1.5 mg, about 0.25 mg to about 1 mg, about 0.25 mg to about 0.9 mg, about 0.25 mg to about 0.8 mg, about 0.25 mg to about 0.7 mg, about 0.25 mg to about 0.6 mg, about 0.25 mg to about 0.6 mg, about 0.25 mg to about 0.5 mg, about 1 mg to about 2.5 mg, about 1 mg to about 2.25 mg, about 1 mg to about 2 mg, about 1 mg to about 1.75 mg, about 1 mg to about 1.5 mg, or about 1 mg to about 1.25 mg of the sKL protein. In some instances, the pharmaceutical composition comprises about 0.25 mg of the sKL protein. In some instances, the pharmaceutical composition comprises about 1 mg of the sKL protein. In some instances, the pharmaceutical composition comprises about 2.5 mg of the sKL protein. In some instances, the pharmaceutical composition comprises 0.25 mg of the sKL protein. In some instances, the pharmaceutical composition comprises 1 mg of the sKL protein. In some instances, the pharmaceutical composition comprises 2.5 mg of the sKL protein. In some instances, the pharmaceutical composition comprises about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, or about 10 mg of the A2M protein and about 0.2 mg, about 0.25 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1.0 mg, about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2.0 mg, about 2.25 mg, or about 2.5 mg of the sKL protein. In some instances, the pharmaceutical composition comprises about 1 mg to about 10 mg, about 1 mg to about 9 mg, about 1 mg to about 8 mg, about 1 mg to about 7 mg, about 1 mg to about 6 mg, about 1 mg to about 5 mg, about 1 mg to about 4 mg, about 1 mg to about 3 mg, about 1 mg to about 2 mg, about 5 mg to about 10 mg, about 5 mg to about 9 mg, about 5 mg to about 8 mg, about 5 mg to about 7 mg, or about 5 mg to about 6 mg of the A2M protein and about 0.25 mg to about 2.5 mg, about 0.25 mg to about 2.25 mg, about 0.25 mg to about 2.0 mg, about 0.25 mg to about 1.75 mg, about 0.25 mg to about 1.5 mg, about 0.25 mg to about 1 mg, about 0.25 mg to about 0.9 mg, about 0.25 mg to about 0.8 mg, about 0.25 mg to about 0.7 mg, about 0.25 mg to Attorney Docket: 51771-0003WO1 about 0.6 mg, about 0.25 mg to about 0.6 mg, about 0.25 mg to about 0.5 mg, about 1 mg to about 2.5 mg, about 1 mg to about 2.25 mg, about 1 mg to about 2 mg, about 1 mg to about 1.75 mg, about 1 mg to about 1.5 mg, or about 1 mg to about 1.25 mg of the sKL protein. In some instances, the pharmaceutical composition comprises about 1 mg of the A2M protein and about 0.25 mg of the sKL protein. In some instances, the pharmaceutical composition comprises about 5 mg of the A2M protein and about 1 mg of the sKL protein. In some instances, the pharmaceutical composition comprises about 10 mg of the A2M protein and about 2.5 mg of the sKL protein. In some instances, the pharmaceutical composition comprises 1 mg of the A2M protein and 0.25 mg of the sKL protein. In some instances, the pharmaceutical composition comprises 5 mg of the A2M protein and 1 mg of the sKL protein. In some instances, the pharmaceutical composition comprises 10 mg of the A2M protein and 2.5 mg of the sKL protein. METHODS OF MAKING A2M AND SKL [00174] Also provided herein are methods of making an A2M protein described herein. [00175] Also provided herein are methods of making an sKL protein described herein. [00176] In some instances, a method of making an A2M protein described herein comprises: (a) culturing a cell comprising a polynucleotide or vector encoding the A2M protein (e.g., under conditions that permit expression of the A2M protein), and (b) isolating the A2M protein. In some instances, the method further comprises formulating the A2M protein as a pharmaceutical composition described herein (e.g., a sterile pharmaceutical composition). In some instances, the method further comprises formulating the A2M protein as a pharmaceutical composition described herein and further comprising an sKL protein. [00177] In some instances, a method of making an sKL protein described herein comprises: (a) culturing a cell comprising a polynucleotide or vector encoding the sKL protein (e.g., under conditions that permit expression of the sKL protein), and (b) isolating the sKL protein. In some instances, the method further comprises formulating the sKL protein as a pharmaceutical composition described herein (e.g., a sterile pharmaceutical composition). In some instances, the method further comprises formulating the sKL protein as a pharmaceutical composition described herein and further comprising an A2M protein. Attorney Docket: 51771-0003WO1 [00178] Polynucleotides, vectors, and cells useful in the methods of making an A2M protein and/or an sKL protein described herein are also provided herein. Thus, provided herein are polynucleotides encoding an A2M protein and/or an sKL protein described herein, vectors comprising said polynucleotides, and cells comprising said polynucleotides or vectors. An exemplary nucleic acid encoding wild type human A2M protein is provided in SEQ ID NO:7 (GenBank Accession No. NM_000014.6; FIG.2A-FIG.2B). An exemplary nucleic acid encoding wild type human KL protein is provided in SEQ ID NO:16 (GenBank Accession No. NM_004795.4; FIG.5A-FIG.5B). In some instances, the polynucleotide is codon-optimized for use in mammalian (e.g., human) cells. Methods of generating polynucleotides and codon- optimization are well-known in the art. [00179] Suitable host cells for expression of an A2M protein described herein are known in the art and include, e.g., prokaryotes (e.g., bacteria, e.g., E. coli), yeast cells, insect cells, and higher eukaryotic (e.g., mammalian) cells. Cell-free translation systems may also be employed. Appropriate cloning and expression vectors for use with bacterial, fungal, yeast, and mammalian cellular hosts, as well as methods of protein production are well-known in the art. [00180] In some instances, an A2M protein and/or an sKL protein described herein is incorporated into an exosome, e.g., for use in the methods described herein. Exosomes are small, membrane-bound vesicles (30-150 nm) that are secreted by cells and can carry various biomolecules, such as, proteins, RNA, and lipids. Exosomes can be engineered to carry drugs, including small molecule drugs, proteins and RNA-based therapies, and deliver them to specific cells in the body. This offers several advantages over traditional drug delivery methods, including improved targeting, reduced toxicity, and the ability to overcome drug resistance mechanisms. Thus, in some instances, exosomes are used for delivery of A2M protein (e.g., comprising the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 4, and/or SEQ ID NO: 6) and/or an sKL protein (e.g., comprising the amino acid sequence of SEQ ID NO: 15) to specific (e.g., target) cells in the body of a subject. In some instances, exosomes carrying A2M and/or sKL protein(s) are generated by encapsulation. For example, A2M and/or sKL protein(s) can be physically incorporated into the exosome's lipid bilayer. Encapsulation of A2M and/or sKL protein(s) into exosomes may protect the A2M and/or sKL protein(s) and allow for targeted delivery of the proteins to specific cells. In some instances, exosomes carrying A2M and/or sKL Attorney Docket: 51771-0003WO1 protein(s) are generated by conjugation. For example, exosomes can be conjugated with A2M and/or sKL protein(s). Conjugation of A2M and/or sKL protein(s) with exosomes may increase specificity and potency of the A2M and/or sKL protein(s). In some instances, exosomes carrying A2M and/or sKL protein(s) are generated by loading the A2M and/or sKL protein(s) into intracellular vesicles. For example, A2M and/or sKL protein(s) can be loaded into intracellular vesicles, which then fuse with exosomes, allowing the proteins to be secreted outside of the cell and delivered to target cells. In some instances, polynucleotides encoding A2M and/or sKL are encapsulated within exosomes, providing protection from degradation and enabling targeted delivery to recipient cells. In some instances, exosomes can deliver A2M and/or sKL protein(s) to target cells by transfection, subsequent expression of the A2M and/or sKL protein(s) and by electroporation. [00181] In some instances, an A2M protein (e.g., comprising the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 4, and/or SEQ ID NO: 6) is incorporated into an exosome. In some instances, an sKL protein (e.g., comprising the amino acid sequence of SEQ ID NO: 15) is incorporated into an exosome. In some instances, an A2M protein and an sKL protein are incorporated into an exosome. Methods of preparing exosomes are known in the art and described in, e.g., Tenchov et al., ACS Nano 2022, 16, 17802-17846, which is incorporated by reference herein in its entirety. An A2M protein and/or an sKL protein can be artificially incorporated into an exosome by several different methods known in the art, including, but not limited to, chemical method, transfection, and/or electroporation. In some instances, an A2M protein and/or an sKL protein is artificially incorporated into an exosome by a chemical method. For incorporation into exosomes by chemical method, an A2M protein and/or an sKL protein can be mixed with exosomes, and then certain chemicals can be added to the mixture to promote the uptake of the A2M protein and/or the sKL protein into the exosome. In some instances, an A2M protein and/or an sKL protein is artificially incorporated into an exosome by transfection. For incorporation of A2M protein and/or sKL protein into exosomes by transfection, exosomes can be mixed with polynucleotides (e.g., DNA) encoding A2M and/or sKL (e.g., polynucleotide encoding A2M, polynucleotide encoding sKL, and/or polynucleotide encoding both A2M and sKL). Following delivery of such exosomes into cells (e.g., using liposomes or electroporation), the polynucleotides encode the A2M and/or sKL proteins, and the A2M and/or sKL proteins can then be packaged into the exosomes. In some instances, an A2M protein and/or an sKL protein Attorney Docket: 51771-0003WO1 is artificially incorporated into an exosome by electroporation. For incorporation of A2M protein and/or sKL protein into exosomes by electroporation, an electric field may be used to introduce large amounts of the A2M protein and/or the sKL protein into exosome(s). METHODS OF USE [00182] This disclosure features methods of using an A2M protein and/or an sKL protein (or pharmaceutical composition comprising said A2M protein and/or sKL protein or pharmaceutical composition comprising A2M protein and sKL protein) described herein for treating a coronavirus (e.g., SARS-CoV-2), treating PASC, treating inflammation, treating cognitive decline (e.g., Alzheimer’s disease), improving cognition, inhibiting senescence, treating bacterial infection, inhibiting an interaction between a SARS-CoV-2 spike protein and an ACE2 protein, inhibiting a coronavirus (e.g., SARS-CoV-2) papain-like protease (PLpro) protein, rejuvenating skin, and cosmetically treating skin in a subject (e.g., human). The terms “treat” or “treating,” as used herein, refer to alleviating, inhibiting, or ameliorating the disease, infection, or condition from which the subject is suffering. In some instances, the methods comprise administering an A2M protein (e.g., a pharmaceutical composition comprising an A2M protein). In some instances, the methods comprise administering an sKL protein (e.g., a pharmaceutical composition comprising an sKL protein). In some instances, the methods comprise administering an A2M protein and an sKL protein (e.g., a pharmaceutical composition comprising an A2M protein and an sKL protein or a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). For example, the methods described herein can comprise administering A2M protein and/or sKL protein that are incorporated (e.g., artificially) into exosomes. In some instances, the administering is subcutaneously. In some instances, the administering is intravenously. In some instances, the administering is topically. In some instances, the administering is intranasally (e.g., by inhalation). [00183] Provided herein is a method of treating a coronavirus infection (e.g., SARs-CoV- 2) in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. In some instances, the A2M protein and Attorney Docket: 51771-0003WO1 the sKL protein are administered to the subject simultaneously as part of a single composition (e.g., pharmaceutical composition). In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of two separate compositions (e.g., a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). In some instances, the A2M protein and the sKL protein are administered to the subject sequentially. For example, in some instances, the A2M protein is administered to the subject first and the sKL protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). As another example, in some instances, the sKL protein is administered to the subject first and the A2M protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein and the sKL protein is a human sKL protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the sKL comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00184] Also provided herein is a method of treating a coronavirus infection (e.g., SARs- CoV-2) in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein. In some instances, the A2M protein used in the methods described herein is in dimeric form. For Attorney Docket: 51771-0003WO1 example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00185] Also provided herein is a method of treating a coronavirus infection (e.g., SARs- CoV-2) in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein described herein. In some instances, the sKL protein is a human sKL protein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00186] Nonlimiting examples of coronaviruses include Alphacoronavirus 1, Avian coronavirus, Bulbul coronavirus HKU11, Equine torovirus, Murine coronavirus, White bream virus, Ball python nidovirus 1, Bat coronavirus CDPHE15, Bat coronavirus HKU10, Beluga whale coronavirus SW1, Betacoronavirus 1, Bovine nidovirus 1, Bovine torovirus, Chinook salmon nidovirus 1, Common moorhen coronavirus HKU21, Coronavirus HKU15, Fathead minnow nidovirus 1, Hedgehog coronavirus 1, Human coronavirus 229E, Human coronavirus HKU1, Human coronavirus NL63, Human torovirus, Middle East respiratory syndrome (MERS) coronavirus, Miniopterus bat coronavirus 1, Miniopterus bat coronavirus HKU8, Mink coronavirus 1, Munia coronavirus HKU13, Night heron coronavirus HKU19, Pipistrellus bat coronavirus HKU5, Porcine epidemic diarrhea virus, Porcine torovirus, Rhinolophus bat coronavirus HKU2, Rousettus bat coronavirus HKU9, severe acute respiratory (SARS) Attorney Docket: 51771-0003WO1 coronavirus (e.g., SARS CoV-2), Scotophilus bat coronavirus 512, SARS-related coronavirus, Thrush coronavirus HKU12, Tylonycteris bat coronavirus HKU4, White-eye coronavirus HKU16, and Wigeon coronavirus HKU20. [00187] In some instances, the coronavirus infection is a SARS-CoV-2 infection. In some instances, the SARS-CoV-2 infection is with an alpha variant (e.g., B.1.1.7 and Q lineages), a beta variant (e.g., B.1.351 and descendent lineages), a gamma variant (e.g., P.1 and descendent lineages), a delta variant (e.g., B.1.617.2 and AY lineages), an epsilon variant (e.g., B.1.427 and B.1.429), an eta variant (e.g., B.1.525), an iota variant (e.g., B.1.526), a kappa variant (e.g., B.1.617.1), 1.617.3, a mu variant (e.g., B.1.621, B.1.621.1), an omicron variant (e.g., B.1.1.529, BA.1, BA.1.1, BA.2, BA.3, BA.4 or BA.5 lineages), or a Zeta variant (e.g., P.2). [00188] In some instances, the coronavirus infection is a SARS-CoV-2 infection. In some instances, the SARS-CoV-2 infection is with an alpha variant. In some instances, the SARS- CoV-2 infection is with a delta variant. [00189] Post-acute sequelae SARS-CoV-2 (PASC) is a syndrome characterized by the persistence of clinical symptoms of infection with SARS-CoV-2 beyond four weeks from initial onset of acute symptoms. Symptoms of SARS-CoV-2 include, but are not limited to, fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion, runny nose, nausea, vomiting, and diarrhea. The working examples herein demonstrate that A2M and sKL are effective at treating SARS-CoV-2. [00190] Thus, also provided herein is a method of treating PASC in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of a single composition (e.g., pharmaceutical composition). In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of two separate compositions (e.g., a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). In some instances, the A2M protein and the sKL protein are administered to the subject sequentially. For example, in some instances, the A2M protein is administered to the subject Attorney Docket: 51771-0003WO1 first and the sKL protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). As another example, in some instances, the sKL protein is administered to the subject first and the A2M protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein and the sKL protein is a human sKL protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the sKL comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00191] Also provided herein is a method of treating post-acute sequelae SARS-CoV-2 (PASC) in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein. In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein Attorney Docket: 51771-0003WO1 comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00192] Also provided herein is a method of treating PASC in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein described herein. In some instances, the sKL protein is a human sKL protein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00193] Also provided herein is a method of treating inflammation in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. In some instances, the inflammation is caused by a toxin (e.g., endotoxin). In some instances, the inflammation is caused by a bacterial infection. In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of a single composition (e.g., pharmaceutical composition). In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of two separate compositions (e.g., a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). In some instances, the A2M protein and the sKL protein are administered to the subject sequentially. For example, in some instances, the A2M protein is administered to the subject first and the sKL protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). As another example, in some instances, the sKL protein is administered to the subject first and the A2M protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, Attorney Docket: 51771-0003WO1 within 3 weeks, within a month). In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein and the sKL protein is a human sKL protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00194] Also provided herein is a method of treating inflammation in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein. In some instances, the inflammation is caused by a toxin (e.g., endotoxin). In some instances, the inflammation is caused by a bacterial infection. In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the Attorney Docket: 51771-0003WO1 administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00195] Also provided herein is a method of treating inflammation in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein described herein. In some instances, the inflammation is caused by a toxin (e.g., endotoxin). In some instances, the inflammation is caused by a bacterial infection. In some instances, the sKL protein is a human sKL protein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00196] Also provided herein is a method of treating a bacterial infection in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of a single composition (e.g., pharmaceutical composition). In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of two separate compositions (e.g., a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). In some instances, the A2M protein and the sKL protein are administered to the subject sequentially. For example, in some instances, the A2M protein is administered to the subject first and the sKL protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). As another example, in some instances, the sKL protein is administered to the subject first and the A2M protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical Attorney Docket: 51771-0003WO1 composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein and the sKL protein is a human sKL protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00197] Also provided herein is a method of treating a bacterial infection in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein. In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00198] Also provided herein is a method of treating a bacterial infection in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein described herein. In some instances, the sKL protein is a Attorney Docket: 51771-0003WO1 human sKL protein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00199] Also provided herein is a method of inhibiting an interaction between a SARS- CoV-2 spike protein and an ACE2 protein, the method comprising contacting a mixture of the SARS-CoV-2 spike protein and the ACE2 protein with an effective amount of an A2M protein described herein and an effective amount of an sKL protein described herein. In some instances, the mixture is simultaneously contacted with the A2M protein and the sKL protein as part of a single composition (e.g., pharmaceutical composition). In some instances, the mixture is simultaneously contacted with the A2M protein and the sKL protein as part of two separate compositions (e.g., a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). In some instances, the mixture is contacted with the A2M protein and the sKL protein sequentially. For example, in some instances, the mixture is first contacted with A2M protein and then the mixture is contacted with sKL protein (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). As another example, in some instances, the mixture is first contacted with sKL protein and then the mixture is contacted with A2M protein (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein and the sKL protein is a human sKL protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID Attorney Docket: 51771-0003WO1 NO:6. In some instances, the sKL comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. [00200] Also provided herein is a method of inhibiting an interaction between a SARS- CoV-2 spike protein and an angiotensin-converting enzyme 2 (ACE2) protein, the method comprising contacting a mixture of the SARS-CoV-2 spike protein and the ACE2 protein with an effective amount of an A2M protein described herein. In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. [00201] Also provided herein is a method of inhibiting an interaction between a SARS- CoV-2 spike protein and an ACE2 protein, the method comprising contacting a mixture of the SARS-CoV-2 spike protein and the ACE2 protein with an effective amount of an sKL protein described herein. In some instances, the sKL protein is a human sKL protein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. [00202] In some instances, the mixture of the SARS-CoV-2 spike protein and the ACE2 protein is on a surface or in the atmosphere. In some instances in which the mixture is on a surface or in the atmosphere, the contacting is via an aerosol. In some instances, the mixture is in vivo (e.g., in a subject, e.g., a human). In some instances in which the mixture is in vivo, the contacting is via topical administration. In some instances in which the mixture is in vivo, the contacting is via intranasal administration. In some instances in which the mixture is in vivo, the contacting is via subcutaneous administration. Attorney Docket: 51771-0003WO1 [00203] In some instances, the inhibiting of the interaction between a SARS-CoV-2 spike protein and an ACE protein is a decrease in the interaction between the SARS-CoV-2 spike protein and the ACE2 protein by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% relative to the interaction between the SARS-CoV-2 spike protein and the ACE2 protein prior to the contacting. Methods of measuring the interaction between a SARS-CoV-2 spike protein and an ACE2 protein are known in the art and described herein (see, e.g., the working examples). [00204] Also provided herein is a method of inhibiting a coronavirus (e.g., SARS-CoV-2) PLpro protein, the method comprising contacting the coronavirus PLpro with an effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. In some instances, the coronavirus PLpro is simultaneously contacted with the A2M protein and the sKL protein as part of a single composition (e.g., pharmaceutical composition). In some instances, the coronavirus PLpro is simultaneously contacted with the A2M protein and the sKL protein as part of two separate compositions (e.g., a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). In some instances, the coronavirus PLpro is contacted with the A2M protein and the sKL protein sequentially. For example, in some instances, the coronavirus PLpro is first contacted with A2M protein and then the mixture is contacted with sKL protein (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). As another example, in some instances, the coronavirus PLpro is first contacted with sKL protein and then the mixture is contacted with A2M protein (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein and the sKL protein is a human sKL protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some Attorney Docket: 51771-0003WO1 instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. [00205] Also provided herein is a method of inhibiting a coronavirus (e.g., SARS-CoV-2) papain-like protease (PLpro) protein, the method comprising contacting the coronavirus PLpro with an effective amount of an A2M protein described herein. In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. [00206] Also provided herein is a method of inhibiting a coronavirus (e.g., SARS-CoV-2) PLpro protein, the method comprising contacting the coronavirus PLpro with an effective amount of an sKL protein described herein. In some instances, the sKL protein is a human sKL protein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. [00207] In some instances, the coronavirus PLpro is on a surface or in the atmosphere. In some instances in which the coronavirus PLpro is on a surface or in the atmosphere, the contacting is via an aerosol. In some instances, the coronavirus PLpro is in vivo (e.g., in a subject, e.g., a human). In some instances in which the coronavirus PLpro is in vivo, the contacting is via topical administration. In some instances in which the coronavirus PLpro is in Attorney Docket: 51771-0003WO1 vivo, the contacting is via intranasal administration. In some instances in which the coronavirus PLpro is in vivo, the contacting is via subcutaneous administration. [00208] In some instances, the inhibiting of the coronavirus PLpro is a decrease in coronavirus PLpro activity by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% relative to the activity of coronavirus PLpro prior to the contacting. Methods of measuring the activity of coronavirus PLpro are known in the art and described herein (see, e.g., the working examples). [00209] The working examples provided herein demonstrate that A2M protein and sKL protein inhibit the activity of cathepsin L. Enveloped viruses such as coronaviruses (e.g., SARS- CoV and MERs-CoV), ebolaviruses, hepatitis E virus, and Nipah virus require cathepsin L for their glycoprotein processing and cleavage. Thus, also provided herein are methods of treating a virus infection, wherein the virus requires cathepsin L for replication. Also provided herein are methods of inhibiting cathepsin L. [00210] In some instances of the method of treating a virus infection in a subject (e.g., human), wherein the virus requires cathepsin L for replication, the method comprises administering to the subject a therapeutically effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of a single composition (e.g., pharmaceutical composition). In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of two separate compositions (e.g., a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). In some instances, the A2M protein and the sKL protein are administered to the subject sequentially. For example, in some instances, the A2M protein is administered to the subject first and the sKL protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). As another example, in some instances, the sKL protein is administered to the subject first and the A2M protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). In some instances, the A2M protein used in the methods Attorney Docket: 51771-0003WO1 described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein and the sKL protein is a human sKL protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00211] In some instances of the method of treating a virus infection in a subject (e.g., human), wherein the virus requires cathepsin L for replication, the method comprises administering to the subject a therapeutically effective amount of an A2M protein described herein. In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the administering is topical. In some instances, the subject is a human. Attorney Docket: 51771-0003WO1 [00212] In some instances of the method of treating a virus infection in a subject (e.g., human), wherein the virus requires cathepsin L for replication, the method comprises administering to the subject a therapeutically effective amount of an sKL protein described herein. In some instances, the sKL protein is a human sKL protein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the administering is intranasal. In some instances, the subject is a human. [00213] Exemplary viruses that require cathepsin L for replication include, enveloped viruses such as coronaviruses (e.g., SARS-CoV and MERs-CoV), ebolaviruses, hepatitis viruses (e.g., hepatitis E virus), Nipah virus, and poxviruses (e.g., vaccinia virus, orthopoxvirus and monkeypox virus). [00214] The working examples provided herein also demonstrate A2M and/or sKL inhibit senescence (see, e.g., Example 18). Thus, also provided herein are methods of inhibiting senescence in a subject (e.g., human) in need thereof, wherein said methods comprise administering to the subject (e.g., human) a therapeutically effective amount of an A2M protein described herein and/or an sKL protein described herein or composition(s) comprising the same. Exemplary biomarkers for inhibiting senescence are known in the art and described in the working examples herein. In some instances, the method comprises administering to the subject a therapeutically effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. Also provided herein are methods of treating cognitive decline (e.g., Alzheimer’s disease) in a subject in need thereof and methods of improving cognition in a subject in need thereof, wherein said methods comprise administering to the subject (e.g., human) a therapeutically effective amount of an A2M protein described herein and/or an sKL protein described herein or composition(s) comprising the same. In some instances, the method comprises administering to the subject a therapeutically effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. In some instance, the subject is at least 50 years, at least 55 years, at least 60 years, at least 70 years, at least 80 years, at least 90 years, or at least 95 years of age. In some instances, the subject is 50 to 100 years, 50 to 90 years, 50 to 80 years, 50 to 70 years, 50 to 60 Attorney Docket: 51771-0003WO1 years, 60 to 100 years, 60 to 90 years, 60 to 80 years, 60 to 70 years, 70 to 100 years, 70 to 90 years, 70 to 80 years, or 80 to 90 years of age. [00215] In some instances, the method further comprises testing the cognitive function of the subject before and/or after administering the A2M protein and/or the sKL protein. For example, in some instances, the method comprises: (a) determining a first cognitive function of the subject, and (b) administering to the subject a therapeutically effective amount of the A2M protein and/or the sKL protein after determining the first cognitive function of the subject. In some instances, the method comprises: (a) determining a first cognitive function of the subject, (b) administering to the subject a therapeutically effective amount of the A2M protein and/or the sKL protein after determining the first cognitive function of the subject, and (c) determining a second cognitive function of the subject after the administering. In some instances, steps (a)-(c) are repeated one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10) times. Methods of determining cognitive function are known in the art and include, e.g., short- and long-term memory testing, evaluation of concentration and attention span, language and communication skills, awareness of time and place (orientation), visuospatial abilities, Ascertain Dementia 8, Functional Activities Questionnare (FAG), mini-Cog, Mini-Mental State Exam (MMSE), Montreal Cognitive Assessment (MoCA), and Neuropsychiatric Inventory Questionnaire (NPI-Q). [00216] In some instances, provided herein is a method of treating cognitive decline (e.g., Alzheimer’s disease) or improving cognition in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of a single composition (e.g., pharmaceutical composition). In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of two separate compositions (e.g., a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). In some instances, the A2M protein and the sKL protein are administered to the subject sequentially. For example, in some instances, the A2M protein is administered to the subject first and the sKL protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a Attorney Docket: 51771-0003WO1 month). As another example, in some instances, the sKL protein is administered to the subject first and the A2M protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein and the sKL protein is a human sKL protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the sKL comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the subject is a human. In some instances, the subject has Alzheimer’s disease. In some instances, the method treats Alzheimer’s disease. In some instance, the subject is at least 50 years, at least 55 years, at least 60 years, at least 70 years, at least 80 years, at least 90 years, or at least 95 years of age. In some instances, the subject is 50 to 100 years, 50 to 90 years, 50 to 80 years, 50 to 70 years, 50 to 60 years, 60 to 100 years, 60 to 90 years, 60 to 80 years, 60 to 70 years, 70 to 100 years, 70 to 90 years, 70 to 80 years, or 80 to 90 years of age. [00217] In some instances, provided herein is a method of treating cognitive decline (e.g., Alzheimer’s disease) or improving cognition in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein. In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein. In some Attorney Docket: 51771-0003WO1 instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the administering is subcutaneous. In some instances, the subject is a human. In some instances, the subject has Alzheimer’s disease. In some instances, the method treats Alzheimer’s disease. In some instance, the subject is at least 50 years, at least 55 years, at least 60 years, at least 70 years, at least 80 years, at least 90 years, or at least 95 years of age. In some instances, the subject is 50 to 100 years, 50 to 90 years, 50 to 80 years, 50 to 70 years, 50 to 60 years, 60 to 100 years, 60 to 90 years, 60 to 80 years, 60 to 70 years, 70 to 100 years, 70 to 90 years, 70 to 80 years, or 80 to 90 years of age. [00218] In some instances, provided herein is a method of treating cognitive decline (e.g., Alzheimer’s disease) or improving cognition in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein described herein. In some instances, the sKL protein is a human sKL protein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is subcutaneous. In some instances, the subject is a human. In some instances, the subject has Alzheimer’s disease. In some instances, the method treats Alzheimer’s disease. In some instance, the subject is at least 50 years, at least 55 years, at least 60 years, at least 70 years, at least 80 years, at least 90 years, or at least 95 years of age. In some instances, the subject is 50 to 100 years, 50 to 90 years, 50 to 80 years, 50 to 70 years, 50 to 60 years, 60 to 100 years, 60 to 90 years, 60 to 80 years, 60 to 70 years, 70 to 100 years, 70 to 90 years, 70 to 80 years, or 80 to 90 years of age. [00219] In some instances, a method described hereinabove is used for treating a subject who has been diagnosed with and/or shows one or more symptoms of a cognitive decline (e.g., Alzheimer’s disease). For example, the methods of the present disclosure can be used for Attorney Docket: 51771-0003WO1 treating a subject who has been diagnosed with and/or shows one or more symptoms of Alzheimer’s disease. [00220] In some instances, one or more cognitive tests is used for diagnosis of a subject with cognitive decline (e.g., Alzheimer’s disease). Additionally, or in the alternative, one or more cognitive tests may be used to determine the impact (e.g., the effect) of the treatment described herein. For example, one or more cognitive tests can be used to diagnose Alzheimer’s disease in a subject, track the progression of Alzheimer’s disease in a subject, and/or monitor the effectiveness of treatment (e.g., method of treatment described herein) on a subject with Alzheimer’s disease. Such cognitive tests may include, without limitations, one or more of the following: (i) Mini-Mental State Examination (MMSE): A brief questionnaire that assesses a person's memory, attention, language, and orientation. (ii) Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog): A more comprehensive test that assesses a wider range of cognitive abilities, including memory, language, attention, and problem-solving. (iii) Clinical Dementia Rating Scale (CDR): A structured interview and examination that assesses a person's cognitive and functional abilities and is used to stage the severity of dementia. (iv) Montreal Cognitive Assessment (MoCA): A brief questionnaire that assesses multiple cognitive domains, including memory, attention, executive function, and language. (v) Neuropsychological tests: A set of tests that assess specific cognitive abilities, such as memory, attention, language, and visuospatial skills. [00221] In some instances, one or more laboratory tests (e.g., blood tests) is used for diagnosis of a subject with cognitive decline (e.g., Alzheimer’s disease). Additionally, or in the alternative, one or more laboratory tests may be used to determine the impact (e.g., the effect) of the treatment described herein. For example, one or more laboratory tests can be used to diagnose Alzheimer’s disease in a subject, track the progression of Alzheimer’s disease in a subject, and/or monitor the effect of treatment (e.g., method of treatment described herein) on a Attorney Docket: 51771-0003WO1 subject with Alzheimer’s disease. Such laboratory tests (e.g., blood tests) may include, without limitations, one or more of the following: (i) Complete blood count (CBC): A test that measures the number and types of cells in the blood. (ii) Comprehensive metabolic panel (CMP): A test that measures levels of electrolytes, glucose, kidney and liver function markers, and other substances in the blood. (iii) Vitamin B12 and folate levels: Tests to measure levels of vitamin B12 and folate, which are important for brain function and the nervous system. (iv) Inflammatory markers: Tests that measure levels of cytokines and other markers of inflammation in the blood, which may play a role in the development of Alzheimer's disease. Such inflammatory markers may include, without limitation, one or more of CRP, IL-6, TNF- α, Von Willebrand factor, fibrinogen, factor VIII, erythrocyte sedimentation rate (ESR), or a composite score comprising different inflammatory markers. (v) Apolipoprotein E (APOE) genotyping: A test to determine a person's APOE genotype, which can affect their risk of developing Alzheimer's disease. [00222] In some instances, a subject is diagnosed with cognitive decline (e.g., Alzheimer's disease) if the vitamin B12 and/or folate level in the subject is lower (e.g., by about 50% or more, such as, by about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or more), as compared to a control vitamin B12 and/or folate level. Control vitamin B12 and/or folate level can comprise any value of vitamin B12 and/or folate level within a range that is clinically accepted as the normal range for vitamin B12 and/or folate level. Additionally, or in the alternative, vitamin B12 and/or folate level in a healthy subject (e.g., a subject not showing cognitive decline, a subject not diagnosed with cognitive decline, and/or a subject not diagnosed with any disease or disorder that might affect vitamin B12 and/or folate level) may be considered as control vitamin B12 and/or folate level. In some instances, following treatment by the methods disclosed herein, the vitamin B12 and/or folate level in a subject may increase by about 50% or more (such as, by about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150%, 175%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, or more), as compared to the vitamin B12 and/or folate level in the subject prior to treatment. In some instances, Attorney Docket: 51771-0003WO1 following treatment by the methods disclosed herein, the vitamin B12 and/or folate level in a subject may increase by about 50% or more (such as, by about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150%, 175%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, or more), as compared to the vitamin B12 and/or folate level in a subject (e.g., a subject with cognitive decline) who has not received the treatment described herein. [00223] In some instances, a subject is diagnosed with cognitive decline (e.g., Alzheimer's disease) if the level of one or more inflammatory markers in the subject is higher (e.g., by about 50% or more, such as, by about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150%, 175%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, or more), as compared to a control level of the inflammatory markers. Control level of inflammatory markers can comprise any level of the inflammatory markers falling within a range that is clinically accepted as the normal range for those inflammatory markers. Additionally, or in the alternative, level of the inflammatory markers in a healthy subject (e.g., a subject not showing cognitive decline, a subject not diagnosed with cognitive decline, and/or a subject not diagnosed with any disease or disorder that might affect the level of the inflammatory markers) may be considered as the control level of the inflammatory markers. In some instances, following treatment by the methods disclosed herein, the level of one or more inflammatory markers in a subject may decrease by about 50% or more (such as, by about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or more), as compared to the level of the inflammatory markers in the subject prior to treatment. In some instances, following treatment by the methods disclosed herein, the level of one or more inflammatory markers in a subject may decrease by about 50% or more (such as, by about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or more), as compared to the level of the inflammatory markers in a subject (e.g., a subject with cognitive decline) who has not received the treatment described herein. [00224] In some instances, one or more biomarker assays is used for diagnosis of a subject with cognitive decline (e.g., Alzheimer’s disease). Additionally, or in the alternative, one or more biomarker assays may be used to determine the impact (e.g., the effect) of the treatment described herein. For example, one or more biomarker assays can be used to diagnose Alzheimer’s disease in a subject, track the progression of Alzheimer’s disease in a subject, and/or monitor the effectiveness of treatment (e.g., method of treatment described herein) on a Attorney Docket: 51771-0003WO1 subject with Alzheimer’s disease. Such biomarker assays may include, without limitations, one or more of the following: (i) Assay for neurofilament light chain (NfL): Neurofilament light chain (NfL) is a type of protein that is found in the nerve cells of the brain and spinal cord. NfL is a component of the cytoskeleton of nerve cells, where it helps to maintain the structure of the cells and facilitate communication between cells. In neurodegenerative disorders, such as, cognitive decline (e.g., Alzheimer’s disease) and multiple sclerosis, the levels of NfL in the blood can be elevated as a result of nerve cell damage and degeneration. Thus, NfL is a promising biomarker for these conditions, providing a non-invasive way to assess the severity of disease and monitor disease progression. NfL levels can be measured in the blood, cerebrospinal fluid, and brain tissue, and correlates well with measures of nerve cell damage, such as brain atrophy, and with measures of cognitive decline. Thus, elevated levels of NfL in blood, cerebrospinal fluid, and/or brain tissue can be a predictor of cognitive decline. Additionally, or in the alternative, NfL level in blood, cerebrospinal fluid, and/or brain tissue can be monitored to assess the efficacy of treatments. (ii) Assay for chitinase-3 (YKL-40): Chitinase-3 has been implicated in the pathogenesis of cognitive decline (e.g., Alzheimer’s disease). Elevated levels of chitinase-3 in blood and brain tissue of Alzheimer's disease patients may contribute to the inflammation and neurodegeneration that occurs in the disease. Chitinase-3 has also been shown to promote the accumulation of amyloid beta, a protein that forms deposits in the brains of Alzheimer's disease patients, and to impair cognitive function in animal models. Elevated levels of chitinase-3 (YKL-40) in blood, cerebrospinal fluid, and/or brain tissue can be a predictor of cognitive decline. Additionally, or in the alternative, chitinase-3 (YKL-40) level in blood, cerebrospinal fluid, and/or brain tissue can be monitored to assess the efficacy of treatments. [00225] In some instances, a subject is diagnosed with cognitive decline (e.g., Alzheimer's disease) if the level of NfL and/or YKL-40 in the subject is higher (e.g., by about 50% or more, such as, by about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 125%, 150%, 175%, 200%, 250%, 300%, 350%, 400%, 450%, 500%, or more), as compared to a control level of NfL and/or YKL-40. Control level of NfL and/or YKL-40 can comprise any level of NfL and/or YKL-40 falling within a range that is clinically accepted as the normal range for NfL and/or YKL-40. Additionally, or in the alternative, level of NfL and/or YKL-40 in a healthy Attorney Docket: 51771-0003WO1 subject (e.g., a subject not showing cognitive decline, a subject not diagnosed with cognitive decline, and/or a subject not diagnosed with any disease or disorder that might affect the level of NfL and/or YKL-40) may be considered as the control level of NfL and/or YKL-40. In some instances, following treatment by the methods disclosed herein, the level of NfL and/or YKL-40 in a subject may decrease by about 50% or more (such as, by about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or more), as compared to the level of NfL and/or YKL- 40 in the subject prior to treatment. In some instances, following treatment by the methods disclosed herein, the level of NfL and/or YKL-40 in a subject may decrease by about 50% or more (such as, by about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or more), as compared to the level of NfL and/or YKL-40 in a subject (e.g., a subject with cognitive decline) who has not received the treatment described herein. [00226] In some instances, for diagnosis and/or monitoring and/or management of cognitive decline (e.g., Alzheimer's disease), one or more of the tests described hereinabove (e.g., cognitive tests, laboratory tests, and/or biomarker assays) is used in combination with other diagnostic tools, including, without limitations, medical (or clinical) examination, neurological examination, and/or imaging studies. For example, one or more of the tests described hereinabove can be used in combination with brain MRI. The specific tests used can depend on the individual subject (e.g., patient) and the stage of their disease. [00227] Also provided herein is a method of rejuvenating skin in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of two separate compositions (e.g., a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). In some instances, the A2M protein and the sKL protein are administered to the subject sequentially. For example, in some instances, the A2M protein is administered to the subject first and the sKL protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). As another example, in some instances, the sKL protein is administered to the subject first and the A2M protein is Attorney Docket: 51771-0003WO1 administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein and the sKL protein is a human sKL protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is topical. In some instances, the subject is a human. [00228] Also provided herein is a method of rejuvenating skin in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein. In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the administering is topical. In some instances, the subject is a human. Attorney Docket: 51771-0003WO1 [00229] Also provided herein is a method of rejuvenating skin in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein described herein. In some instances, the sKL protein is a human sKL protein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is topical. In some instances, the subject is a human. [00230] Also provided herein is a method of cosmetically treating skin in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein and a therapeutically effective amount of an sKL protein described herein. In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of a single composition (e.g., pharmaceutical composition). In some instances, the A2M protein and the sKL protein are administered to the subject simultaneously as part of two separate compositions (e.g., a pharmaceutical composition comprising an A2M protein and a pharmaceutical composition comprising an sKL protein). In some instances, the A2M protein and the sKL protein are administered to the subject sequentially. For example, in some instances, the A2M protein is administered to the subject first and the sKL protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). As another example, in some instances, the sKL protein is administered to the subject first and the A2M protein is administered to the subject second (e.g., within 5 minutes, within 1 hour, within 2 hours, within 1 day, within 2 days, within 3 days, within 1 week, within 2 weeks, within 3 weeks, within a month). In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein and the sKL protein is a human sKL protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M Attorney Docket: 51771-0003WO1 protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is topical. In some instances, the subject is a human. [00231] Also provided herein is a method of cosmetically treating skin in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an A2M protein described herein. In some instances, the A2M protein used in the methods described herein is in dimeric form. For example, in some instances, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or 100% of the A2M protein in a pharmaceutical composition used in a method described herein is in dimeric form. In some instances, the A2M protein is a human A2M protein. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein comprises the amino acid sequence of SEQ ID NO:6. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:2. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:4. In some instances, the A2M protein consists of the amino acid sequence of SEQ ID NO:6. In some instances, the administering is topical. In some instances, the subject is a human. [00232] Also provided herein is a method of cosmetically treating skin in a subject (e.g., human) in need thereof, the method comprising administering to the subject a therapeutically effective amount of an sKL protein described herein. In some instances, the sKL protein is a human sKL protein. In some instances, the sKL protein comprises the amino acid sequence of SEQ ID NO:15. In some instances, the sKL protein consists of the amino acid sequence of SEQ ID NO:15. In some instances, the administering is topical. In some instances, the subject is a human. [00233] In some instances, a method of rejuvenating skin or cosmetically treating skin described herein results in an increase (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least Attorney Docket: 51771-0003WO1 100%, at least 200%, or at least 500%) in the level (e.g., protein or mRNA) of SIRT2, SIRT4, SIRT6, lamin B1 and/or collagen III and/or a decrease (e.g., by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or 100) in the level of one or more of p16, p21, p53, and beta-galactosidase in skin cells compared to the level (e.g., protein or mRNA) of SIRT2, SIRT4, SIRT6, lamin B1 and/or collagen III and/or the level of one or more of p16, p21, p53, and beta-galactosidase, respectively, in skin cells prior to administration of the A2M and/or sKL. [00234] Specific dosage and treatment regimens for any particular subject (e.g., human) will depend upon a variety of factors, including the activity of the specific agent (e.g., an A2M protein and/or an sKL protein) employed, the age, body weight, general health status, sex, diet, time of administration, rate of excretion, drug combination, the severity and course of the disease, condition or symptoms, the subject’s disposition to the disease, condition or symptoms, and the judgment of the treating physician. [00235] An effective amount can be administered in one or more administrations, applications or dosages. A therapeutically effective amount of a therapeutic agent (e.g., an A2M protein or an sKL protein) (i.e., an effective dosage) depends on the therapeutic agent selected. The skilled artisan will appreciate that certain factors may influence the dosage and timing required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health and/or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of an agent described herein (e.g., an A2M protein or an sKL protein) can include a single treatment or a series of treatments. For example, effective amounts can be administered at least once (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 times). [00236] A subject treated according to the methods described herein includes animals such as a mammal, e.g., a non-primate (e.g., cows, pigs, horses, cats, dogs, rats, mice, etc.) or a primate (e.g., monkey and human). In some instances, the subject is a human. [00237] In some instances of the foregoing methods comprising administering an A2M protein and an sKL protein or contacting a substance or mixture with an A2M protein and an sKL protein, the A2M protein and the sKL protein are at an A2M:sKL ratio of about 1:1, about 2:1, about 2.5:1, about 3:1, about 4:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1, about Attorney Docket: 51771-0003WO1 10:1, about 11:1, about 12:1, about 20:1, about 30:1, about 40:1, about 50:1, about 60:1, about 70:1, about 80:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, or about 1:10. In some instances, the A2M protein and the sKL protein are administered or contacted at an A2M:sKL ratio of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. In some instances, the A2M protein and the sKL protein are administered or contacted at an A2M:sKL ratio of 1:1. In some instances, the A2M protein and the sKL protein are administered or contacted at an A2M:sKL ratio of 2.5:1. In some instances, the A2M protein and the sKL protein are administered or contacted at an A2M:sKL ratio of 5:1. In some instances, the A2M protein and the sKL protein are administered or contacted at an A2M:sKL ratio of 10:1. In some instances, the A2M protein and the sKL protein are administered or contacted at an A2M:sKL ratio of 11:1. In some instances, the A2M protein and the sKL protein are administered or contacted at an A2M:sKL ratio of 12:1. In some instances, the A2M protein and the sKL protein are administered or contacted at an A2M:sKL ratio of 50:1. The term “about” in the context of an A2M:sKL ratio means +/-10% of the recited value. In some instances the A2M protein and the sKL protein are in a single composition (e.g., pharmaceutical composition). In some instances, the A2M protein and the sKL protein are in two separate compositions (e.g., two separate pharmaceutical compositions). [00238] In some instances of a method described herein, the therapeutically effective amount of the A2M protein is about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, or about 10 mg. In some instances, the therapeutically effective amount of the A2M protein is about 1 mg to about 10 mg, about 1 mg to about 9 mg, about 1 mg to about 8 mg, about 1 mg to about 7 mg, about 1 mg to about 6 mg, about 1 mg to about 5 mg, about 1 mg to about 4 mg, about 1 mg to about 3 mg, about 1 mg to about 2 mg, about 5 mg to about 10 mg, about 5 mg to about 9 mg, about 5 mg to about 8 mg, about 5 mg to about 7 mg, or about 5 mg to about 6 mg. In some instances, the therapeutically effective amount of the A2M protein is about 1 mg. In some instances, the therapeutically effective amount of the A2M protein is about 5 mg. In some instances, the therapeutically effective amount of the A2M protein is about 10 mg. In some instances, the therapeutically effective amount of the A2M protein is 1 mg. In some instances, the therapeutically effective amount of the A2M protein is 5 mg. In some instances, the therapeutically effective amount of the A2M protein is 10 mg. In some instances of a method described herein, the therapeutically Attorney Docket: 51771-0003WO1 effective amount of the sKL protein is about 0.2 mg, about 0.25 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1.0 mg, about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2.0 mg, about 2.25 mg, or about 2.5 mg. In some instances, the therapeutically effective amount of the sKL protein is about 0.25 mg to about 2.5 mg, about 0.25 mg to about 2.25 mg, about 0.25 mg to about 2.0 mg, about 0.25 mg to about 1.75 mg, about 0.25 mg to about 1.5 mg, about 0.25 mg to about 1 mg, about 0.25 mg to about 0.9 mg, about 0.25 mg to about 0.8 mg, about 0.25 mg to about 0.7 mg, about 0.25 mg to about 0.6 mg, about 0.25 mg to about 0.6 mg, about 0.25 mg to about 0.5 mg, about 1 mg to about 2.5 mg, about 1 mg to about 2.25 mg, about 1 mg to about 2 mg, about 1 mg to about 1.75 mg, about 1 mg to about 1.5 mg, or about 1 mg to about 1.25 mg. In some instances, the therapeutically effective amount of the sKL protein is about 0.25 mg. In some instances, the therapeutically effective amount of the sKL protein is about 1 mg. In some instances, the therapeutically effective amount of the sKL protein is about 2.5 mg. In some instances, the therapeutically effective amount of the sKL protein is 0.25 mg. In some instances, the therapeutically effective amount of the sKL protein is 1 mg. In some instances, the therapeutically effective amount of the sKL protein is 2.5 mg. In some instances, the therapeutically effective amount of the A2M protein is about 1 mg, about 2 mg, about 3 mg, about 4 mg, about 5 mg, about 6 mg, about 7 mg, about 8 mg, about 9 mg, or about 10 mg and the therapeutically effective amount of the sKL protein is about 0.2 mg, about 0.25 mg, about 0.3 mg, about 0.4 mg, about 0.5 mg, about 0.6 mg, about 0.7 mg, about 0.8 mg, about 0.9 mg, about 1.0 mg, about 1.25 mg, about 1.5 mg, about 1.75 mg, about 2.0 mg, about 2.25 mg, or about 2.5 mg. In some instances, the therapeutically effective amount of the A2M protein is about 1 mg to about 10 mg, about 1 mg to about 9 mg, about 1 mg to about 8 mg, about 1 mg to about 7 mg, about 1 mg to about 6 mg, about 1 mg to about 5 mg, about 1 mg to about 4 mg, about 1 mg to about 3 mg, about 1 mg to about 2 mg, about 5 mg to about 10 mg, about 5 mg to about 9 mg, about 5 mg to about 8 mg, about 5 mg to about 7 mg, or about 5 mg to about 6 mg and the therapeutically effective amount of the sKL protein is about 0.25 mg to about 2.5 mg, about 0.25 mg to about 2.25 mg, about 0.25 mg to about 2.0 mg, about 0.25 mg to about 1.75 mg, about 0.25 mg to about 1.5 mg, about 0.25 mg to about 1 mg, about 0.25 mg to about 0.9 mg, about 0.25 mg to about 0.8 mg, about 0.25 mg to about 0.7 mg, about 0.25 mg to about 0.6 mg, about 0.25 mg to about 0.6 mg, about 0.25 mg to about 0.5 mg, about 1 mg to about 2.5 mg, about 1 mg to about 2.25 mg, about 1 mg to about 2 Attorney Docket: 51771-0003WO1 mg, about 1 mg to about 1.75 mg, about 1 mg to about 1.5 mg, or about 1 mg to about 1.25 mg. In some instances, the therapeutically effective amount of the A2M protein is about 1 mg and the therapeutically effective amount of the sKL protein is about 0.25 mg. In some instances, the therapeutically effective amount of the A2M protein is about 5 mg and the therapeutically effective amount of the sKL protein is about 1 mg. In some instances, the therapeutically effective amount of the A2M protein is about 10 mg and the therapeutically effective amount of the sKL protein is about 2.5 mg. In some instances, the therapeutically effective amount of the A2M protein is 1 mg and the therapeutically effective amount of the sKL protein is 0.25 mg. In some instances, the therapeutically effective amount of the A2M protein is 5 mg and the therapeutically effective amount of the sKL protein is 1 mg. In some instances, the therapeutically effective amount of the A2M protein is 10 mg and the therapeutically effective amount of the sKL protein is 2.5 mg. In some instances, the frequency of the administration of the A2M protein, the sKL protein, or the combination thereof is for a period of two weeks, four weeks, 3 months, 6 months, or indefinitely. In some instances, the A2M protein, the sKL protein, or the combination thereof is/are administered every day (e.g., for a period of two weeks, three weeks, four weeks, 3 months, 6 months, or indefinitely). In some instances, the A2M protein, the sKL protein, or the combination thereof is/are administered every other day (e.g., for a period of two weeks, three weeks, four weeks, 3 months, 6 months, or indefinitely). In some instances, the A2M protein, the sKL protein, or the combination thereof is/are administered every three days (e.g., for a period of two weeks, three weeks, four weeks, 3 months, 6 months, or indefinitely). In some instances, the A2M protein, the sKL protein, or the combination thereof is/are administered are administered once a week (e.g., for a period of two weeks, three weeks, four weeks, 3 months, 6 months, or indefinitely). In some instances, each administration is once a day. For example, in some instances, the A2M protein, the sKL protein, or the combination thereof is/are administered once daily every day (e.g., for a period of two weeks, three weeks, four weeks, 3 months, 6 months, or indefinitely). In some instances, each administration is twice a day. For example, in some instances, the A2M protein, the sKL protein, or the combination thereof is/are administered twice daily every day (e.g., for a period of two weeks, three weeks, four weeks, 3 months, 6 months, or indefinitely). The skilled artisan will appreciate that certain factors may influence the dosage and timing required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health Attorney Docket: 51771-0003WO1 and/or age of the subject, and other diseases present. For instance, for an acute respiratory condition, the administration of the A2M protein, the sKL protein, or the combination thereof may be for a period of two weeks. For instance, for an acute inflammatory condition, the administration of the A2M protein, the sKL protein, or the combination thereof may be for a period of four weeks. For instance, for a cognitive disorder, the administration of the A2M protein, the sKL protein, or the combination thereof may be indefinitely. In some instances, the A2M protein, the sKL protein, or the combination thereof is administered subcutaneously. In some instances, the A2M protein, the sKL protein, or the combination thereof is administered topically. [00239] Also provided herein are uses of an A2M protein and/or an sKL protein in the manufacture of a medicament for, e.g., treating a coronavirus infection, treating post-acute sequelae SARS-CoV-2 (PASC), treating inflammation, inhibiting an interaction between a SARS-CoV-2 spike protein and an angiotensin-converting enzyme 2 (ACE2) protein, inhibiting a coronavirus (e.g., SARS-CoV-2) papain-like protease (PLpro) protein, rejuvenating skin, or cosmetically treating skin in a subject (e.g., human). EXAMPLES Example 1: Anti-Inflammatory and Anti-Viral Effect of A2M and/or sKL This example assesses the anti-inflammatory and anti-viral effect of A2M and sKL. As used in the examples, “IBZ” refers to combination of A2M and sKL. [00240] To evaluate the anti-inflammatory effect of A2M and/or sKL, PBMCs were isolated from blood of two adult healthy donors with Ficoll and resuspended in RPMI complete media (RPMI, 10%FBS, 1%Pen-Strep, 1% L-Glu, 2% HEPES). 30,000 cells were seeded in each well of 96 well plate. Cells were treated with three different combined concentrations of A2M and sKL and/or Wortmannin (WM): IBZ-2 (2 µM A2M plus 0.2 µM sKL); IBZ-1 (1 µM A2M plus 0.1 µM sKL); IBZ-0.5 (0.5 µM A2M plus 0.05 µM sKL); WM-10 (Wortmannin 10 µM); WM-1 (Wortmannin 1 µM); and WM-0.1 (Wortmannin 0.1 µM). Cells were incubated at 37 °C, 5% CO2 for 24 hours. The next day, lipopolysaccharide (LPS; 0.1 µg/mL) and phytohemagglutinin (PHA) were added for activation of PBMCs. After 4 hours and 24 hours of Attorney Docket: 51771-0003WO1 LPS stimulation, cell supernatants were collected for IL-6 (FIGs.7-10) and TNF-alpha (FIGs. 11-14) ELISA. At 24 hours, MTT assay (FIG.15 and FIG.16) was performed on treated PBMCS. All results are mean ±SD of three different replicates. *P<0.05, **P<0.01, ****P<0.0001 and ns means not significant using student’s t-test relative to PBMCs activated with LPS. [00241] At 4 and 24 hours, IBZ1 (*P<0.05 and **P<0.01 for Donor 1 at 4 hours and 24 hours **P<0.01 for Donor 2 at 4 hours), and/or IBZ2 (****P<0.0001 at 4 hours & **P<0.01 for Donor 1 at 24 hours) independently activated IL-6 (FIGs.7-10) in PBMC of both donors (no added PHA/LPS). TNFα was minorly increased at 4 hours (FIG.11) in donor 1 (IBZ2, no added PHA/LPS). There was significant suppression (p<0.01) of both LPS induced IL-6 and TNFα in Donor 1 (FIG.11) at IBZ-0.5 (low dose). Wortmannin control showed significant suppression of LPS activation with low toxicity. Example 2: Effect of A2M and/or sKL on cytokine release in human monocytes [00242] This example assesses the effect of A2M and sKL, alone or in combination, on cytokine release in human monocytes. Briefly, human monocytes were isolated from peripheral blood mononuclear cells (PBMCs) from healthy human donors. The human monocytes were treated with sKL, A2M, and/or LRPAP in the presence or absence of LPS for one hour at 37 °C. Cells were subsequently stimulated with LPS (at a final concentration of 10 ng/ml) for an additional, 6, 24, or 48 hours, or treated with buffer control. 10 ng/ml of LPS was used as a high signal control. For a low signal control, cells were treated with culture medium only. Cell supernatants were harvested at the indicated time points and frozen immediately at -80 °C until signal detection by cytometric bead array (CBA) assay (BD Biosciences). CBA assay measured TNF, IL-6, IL-10, IL-8, IL-1β, IL-12p70, Il-4, IFN-γ, MCP-1, and CCL5 according to the manufacturer’s instructions. Supernatants were thawed and diluted five-fold for TNF, IL-6, IL- 10, IL-8, IL-1β, and IL-12p70 and primary liquid was used for IL-4, IFN-γ, MCP-1, and CCL5. Cells were collected for viability assays. Treatment with sKL, A2M, and/or LRPAP, alone or in combination, had no effect on monocyte cell viability (data not shown). [00243] FIGs.17-19 present data from a first donor at 6, 24, and 48 hours, respectively. FIGs.20-22 present data from a second donor at 6, 24, and 48 hours, respectively. FIGs.23-25 Attorney Docket: 51771-0003WO1 present data from a third donor at 6, 24, and 48 hours, respectively. LPS significantly stimulated the expression of MCP-1, CCL-5, IL-1beta, IL-6, IL-8, IL-10 and TNFa except IL-4,TNFa and IL-12p70. Statistical data are provided in Tables 1-9 below. [00244] Table 1. Statistical data for FIG.17. Kruskal-Wallis test: LPS for 6 hrs IL-4 IFN-γ MCP-1 CCL5 IL-8 IL-1β IL-6 IL-10 TNF-α IL-12p70 P value 0.12 0.3274 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 * s 05 p70 * Pre vs post LPS - sKL(0.1 μM) ns ns *** *** ns ns * ns ns *** * * * * [00245] Table 2. Statistical data for FIG.18. Kruskal-Wallis test: LPS for 24 hrs I _{L-4 IFN-γ MCP-1 CCL5 IL-8 IL-1} ^β _{IL-6 IL-10 TNF-} ^α _IL-12p70 P value 0.0845 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 0.4625 s o ₄ 81 p70 . s ** *** *** ** * s s s s s [00246] Table 3. Statistical data for FIG.19. Kruskal-Wallis test: LPS for 48 hrs I _{L-4 IFN-γ MCP-1 CCL5 IL-8 IL-1} ^β _{IL-6 IL-10 TNF-} ^α _IL-12p70 001 * s 4 99 p70 P _{re vs post LPS - sKL(0 2 μM) ns} ^{** *** *** ***} _** ^{*** ***} _* ^{*** * *} * * * Attorney Docket: 51771-0003WO1 *p≤0.05, **p≤0.01 and *** p≤0.001 [00247] Table 4. Statistical data for FIG.20. Kruskal-Wallis test: LPS for 6 hrs IL-4 IFN-γ MCP-1 CCL5 IL-8 IL-1β IL-6 IL-10 TNF-α IL-12p70 P value 0.1309 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 0.5757 Exact or approximate P value? Gaussian Approximation s o 4 42 2p70 s P LP KL 1 M *** *** ** ** s s s s s [00248] Table 5. Statistical data for FIG.21. Kruskal-Wallis test: LPS for 24 hrs IL-4 IFN-γ MCP-1 CCL5 IL-8 IL-1β IL-6 IL-10 TNF-α IL-12p70 P value 0.2771 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 0.086 s o 4 39 70 [00249] Table 6. Statistical data for FIG.22. Kruskal-Wallis test: LPS for 48 hrs IL-4 IFN-γ MCP-1 CCL5 IL-8 IL-1β IL-6 IL-10 TNF-α IL-12p70 5 _{5 s} o 4 .7 p70 *** *** *** *** *** *** ** s s s s s s Attorney Docket: 51771-0003WO1 [00250] Table 7. Statistical data for FIG.23. Kruskal-Wallis test: LPS for 6 hrs IL-4 IFN-γ MCP-1 CCL5 IL-8 IL-1β IL-6 IL-10 TNF-α IL-12p70 P value 0.1309 < 0.0001 < 0.0001 0.0001 < 0.0001 < 0.0001 0.0001 < 0.0001 < 0.0001 0.0038 Exact or a roximate P value? Gaussian A roximation s 4 64 p70 _{. s Pre vs post LPS - sKL(0.1 μM) ns **} ^{ns ** *** *** *** *** ***} _ns s s s s [00251] Table 8. Statistical data for FIG.24. Kruskal-Wallis test: LPS for 24 hrs I _{L-4 IFN-γ MCP-1 CCL5 IL-8 IL-1} ^β _{IL-6 IL-10 TNF-} ^α _IL-12p70 P value 0.554 0.0006 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 0.7963 s o 4 85 p70 s *** *** *** *** *** *** *** s s s s s [00252] Table 9. Statistical data for FIG.25. Kruskal-Wallis test: LPS for 48 hrs I _{L-4 IFN-γ MCP-1 CCL5 IL-8 IL-1} ^β _{IL-6 IL-10 TNF-} ^α _{IL-12p70 12} s o 4 8 ₃ p70 Pre vs post LPS - sKL(02 μM) ns * *** *** *** *** *** ns * ns s s s s s Attorney Docket: 51771-0003WO1 [00253] For IL-4, A2M and sKL, alone or in combination, showed no significant effect on the cytokine response at 6, 24 and 48 hours. [00254] For IFN-γ, A2M and sKL, alone or in combination, showed significant effect on the cytokine response at 6, 24 and 48 hours in donor 2 and 3. [00255] For MCP-1, A2M and sKL, alone or in combination, showed significant effect on the cytokine response at 6, 24 and 48 hours in all donors. Synergism was evident at 6 and 48 hours. At 6 hours (FIG.17, FIG.20, and FIG.23), the synergistic suppression of MCP-1 is evident when a combination of A2M 0.5 uM + 0.1 uM sKL were used. Administration of the higher dose of A2M 1.0 uM + 0.2 uM sKL resulted in marked and significant suppression relative to the LPS positive control and is an example of synergism (FIG.17). At 48 hours (FIG. 19), the synergistic suppression of MCP-1 is evident when a combination of A2M 0.5 uM + 0.1 uM sKL are used. The level of suppression of MCP-1 is significant when individually administered relative to the positive LPS control. Administration of the higher dose of A2M 1.0 uM + 0.2 uM sKL resulted in marked and significant suppression relative to the LPS positive control and is an example of synergism. [00256] For CCL-5, A2M and sKL, alone or in combination, showed significant effect on the cytokine response at 6 hours in all donors. After 24 hours, the effect of SKL disappeared. Synergism was evident at 6 hours. At 6 hours (FIG.17), administration of the higher dose of A2M 1.0 uM + 0.2 uM sKL resulted in a more marked and significant suppression relative to the LPS positive control and is an example of synergism. [00257] For IL-8, A2M and sKL, alone or in combination, showed no effect on the cytokine response at 6 and 24 hours in all donors. A2M alone showed significant effect on the cytokine at 48 hours. [00258] For IL-1β, A2M and sKL, alone or in combination, showed significant effect on the cytokine response at 6, 24 and 48 hours in donor 2 and 3. [00259] For IL-6, A2M and sKL, alone or in combination, showed significant effect on the cytokine response at 6 hours in all donors. After 24 hours, the effect disappeared. Synergism was evident at 6 and 48 hours. At 6 hours (FIG.17 and FIG.20), the synergistic suppression of MCP-1 is evident when a combination of A2M 0.5 uM + 0.1 uM sKL were used. The level of suppression of MCP-1 is significant when individually administered relative to the positive LPS control. Administration of the higher dose of A2M 1.0 uM + 0.2 uM sKL resulted in a more Attorney Docket: 51771-0003WO1 marked and significant suppression relative to the LPS positive control and is an example of synergism (FIG.17). At 48 hours (FIG.19), administration of the higher dose of A2M 1.0 uM + 0.2 uM sKL resulted in a more marked and significant suppression relative to the LPS positive control and is an example of synergism. [00260] For IL-10, sKL alone or combined with A2M at high concentration showed significant effect on the cytokine response at 6, 24 and 48 hours in all donors. Synergism was evident at 6 and 48 hours. At 6 hours (FIG.17), administration of the higher dose of A2M 1.0 uM + 0.2 uM sKL resulted in a more marked and significant suppression relative to the LPS positive control and is an example of synergism. In another donor at 6 hours (FIG.19), administration of the lower dose of A2M 0.5 uM + 0.1 uM sKL resulted in a more marked and significant suppression relative to the LPS positive control and is an example of synergism once again. At 48 hours (FIG.19), administration of the higher dose of A2M 1.0 uM + 0.2 uM sKL resulted in a more marked and significant suppression relative to the LPS positive control and is an example of synergism. [00261] For TNF-α, A2M and sKL, alone or combined at high dose, showed significant effect on the cytokine response at 6 hours in all donors. After 6 hours, the TNF-α levels were decreased in all donors. [00262] For IL-12p70, A2M and sKL, alone or in combination, showed no effect on the cytokine response at 6, 24 and 48 hours except in donor 1. [00263] These data also highlight the impact of LRPAP. LRPAP is an inhibitor of A2M (specifically, at its cognate receptor [LRP-1]). These data demonstrate the importance of A2M- mediated LRP-1 inhibition of certain cytokines at certain time points designated. Example 3: Effect of A2M and/or sKL on activation of the NLRP3 inflammasome in human macrophages [00264] This example assesses the effect of A2M and sKL, alone or in combination, on activation of the NLRP3 inflammasome in human macrophages. The NLRP3 inflammasome plays a critical role in this inflammation. [00265] Briefly, human monocytes were isolated from human PBMCs. GM-CSF was added to stimulate monocytes and macrophages were harvested. Differentiated human Attorney Docket: 51771-0003WO1 macrophages were stimulated with LPS for 3.5 hours and then treated with A2M and/or sKL. Cells were then stimulated with ATP for 45 minutes. [00266] After ATP stimulation, cell supernatants were collected, centrifuged, and frozen at -80 °C until signal detection by ELISA. Supernatants were thawed at RT and assayed individually using human IL-1β ELISA kit from BD to measure IL-1β concentration, according to the manufacturer’s instructions. [00267] MCC950 was used as a control inhibitor of NLRP3. [00268] Results are depicted in FIGs.26-29. [00269] The reference compound, MCC950, obtained potent inhibitory effect on the cytokine release of human IL-1β, and its IC50 values were within the range of historic data (0.01671 ± 0.0079 µM for macrophages IL-1β ELISA assay). [00270] IL-1β was impaired by MCC950, which IC50 values were determined as 0.009 µM and 0.014 µM individually in separate two plates, involved in testing SKL & A2M alone or combination. A2M showed no inhibitory effect on the release of IL-1β. While SKL generated an inhibitory effect on HMDM when tested alone, with its IC50 was determined as 0.18 µM. In the combination test of SKL plus A2M on HMDM, sKL also generated the anti-inflammatory effect on HMDM with IC50 was determined as 0.5 µM. SKL combined with A2M generated above 50% inhibition rate at the highest dose of 0.5 µM. This result also indicated that the addition of A2M had some inhibiting effect to the anti-inflammatory effects of SKL on human macrophages. [00271] This example demonstrates that the addition of A2M had an additional effect on the anti-inflammatory response induced by SKL on human macrophages. At the highest dose of 0.2 μM, SKL showed partial anti-inflammatory effect, with inhibition rate over 50%. Whilst the lower doses of SKL were not effective in inhibiting the LPS response, and the addition of A2M did not alter this effect. It is worth noting that IL-1β was also the least sensitive to A2M- mediated inhibition. Example 4: A2M and sKL combination therapy in LPS mouse model [00272] Lipopolysaccharide (LPS) is produced by most Gram-negative bacteria and studied extensively as one of bacterial surface molecules glycolipid, with ability to stimulate the Attorney Docket: 51771-0003WO1 immune system, for which it was commonly known as endotoxin. In vivo, LPS can induce inflammation and tissue injury resulting from Gram-negative bacterial infection, and the pathology and symptoms are similar to clinical manifestation of some diseases in human such as neuroinflammation, lung injury and liver injuries. The purpose of this experiment was to test the efficacy of A2M and sKL in mice challenged with LPS. [00273] 60 male C57BL/6 mice, aged 8-9 weeks, were acclimatized for one week prior to the treatment. All the mice were divided into 2 groups based on body weight: Control (LPS + saline) group (Group 1); Active (LPS + A2M + sKL) group (Group 2). All mice were challenged intraperitoneally with two LPS injections of 200 μg in 0.1 mL deionized water separated by a 27 hour interval (T=0 hour and T=+27 hours). Each mouse was received intraperitoneal administration of 100 μL A2M and sKL (containing 0.72 mg of A2M and 5.6 μg of sKL) or saline at 12 hours pre-LPS (T=-12 hours) and 12 hours post the first LPS challenge (T=+12 h). During the experiment, the health status of the animals was monitored twice daily (every 12 hours) for 5 days and survival data was recorded. Serum was collected at 6 hours from some mice following the second LPS injection (T=+33 h) and assayed for murine cytokines (IL-1β, IL- 4, IL-6, IL-8, IL-10, IL-12, IL-18, IFN-γ, MCP-1, CXCL2, CCL1, CCL5 and TNF-α) by ELISA. [00274] The data from this study indicated that two injections of LPS (200 μg/time/mouse) could conspicuously induce acute inflammation model in C57BL/6 mice. [00275] The mortality of control group (Group 1) reached 100 % within 48 hours after the first LPS injection, while treatment with A2M and sKL effectively reduced mortality and improved survival rate during this experiment (FIG.30). [00276] Compared with control group (Group 1), A2M/sKL group (Group 2) significantly reduced the levels of IL-1β, IL-4 and CXCL-2 (FIGS.31A, 31B, and 31J). The levels of IL-10, IL-12, IL-18, IFN-γ, MCP-1, CCL5 and TNF-α in mice of Group 2 was less than that of Group 1, but there was no statistical difference (P > 0.05) (FIGS.31E-31I, 31L, and 31M). Analysis of IL-6, IL-8 and CCL-1 level indicated no obvious differences (FIGS.31C, 31D, 31K). The results showed that combination treatment with A2M and sKL reduces inflammatory reaction. Without being bound by any particular theory, it is hypothesized that A2M and sKL reduce the inflammatory reaction mainly by means of decreasing murine cytokines level. Attorney Docket: 51771-0003WO1 [00277] In conclusion, combination treatment with A2M and sKL has a good inhibitory effect on LPS induced mouse inflammation model. Example 5: Anti-viral effect of A2M and sKL in vitro [00278] This example assess the antiviral effect of A2M and sKL, alone or in combination, against SARS-CoV-2 in VERO E6 cells and in Calu-3 cells. [00279] First, the cytotoxicity of A2M and sKL in VERO E6 cells and in Calu-3 cells was investigated. Briefly, Vero E6 cells and Calu-3 cells were grown in DMEM medium without phenol red (D1145; Sigma Aldrich) supplemented with 10% FBS (Eurobio-Scientific), 1mM sodium pyruvate (S8636; Sigma Aldrich), L-Glutamine (G7513; Sigma Aldrich) and Penicillin- Streptomycin solution (P0781; Sigma Aldrich). Cells were plated and subsequently treated with A2M and/or sKL and incubated at 37 °C and 5% CO2 for 24 or 48 hours. Cells were stained with Image-iT DEAD Green Viability Stain (Invitrogen I10291) and with MitoTracker Orange (Invitrogen M7510) for 30 minutes at 37°C. Cells were fixed with 4% formalin (Sigma) for 10 minutes at room temperature, washed with phosphate buffered saline (PBS) and incubated with PBS Hoechst 33342 (1mg/mL). Data acquisition by high content microscopy was performed on a Thermo CellInsight CX7 HCS microscope using a compartmental analysis algorithm. Results were extracted, normalized over the vehicle-treated condition, and expressed as the average of three independent wells +/- SD. CC50/CC95 were calculated using the Combenefit software (Di Veroli GY, Fornari C, Wang D, Mollard S, Bramhall JL, Richards FM, Jodrell DI. Combenefit: an interactive platform for the analysis and visualization of drug combinations. Bioinformatics. 2016 Sep 15;32(18):2866-8. Epub 2016 Apr 25. DOI; PubMed: 27153664; PubMed Central: PMC5018366) [00280] The EC ₅₀ for A2M in VERO E6 cells was calculated to be 10.7 µM. The EC ₅₀ for sKL in VERO E6 cells was calculated to be 0.814 µM. The EC50 for sKL in Calu-3 cells was calculated to be 0.814 µM. [00281] Next, the antiviral activity was evaluated. VERO E6 and Calu-3 cells were cultured as described above for the cytotoxicity studies. VERO E6 cells were infected with SARS-CoV-2 at an MOI of 0.001. Calu-3 cells were infected with SARS-CoV-2 at an MOI of 0.01. To assess the antiviral activity of both A2M and sKL compounds in Vero E6 cells, the Attorney Docket: 51771-0003WO1 cells were treated 1 hour before infection with media containing Remdesivir ("RMD"; 6 µM; positive control), A2M at 1 or 0.5 µM, sKL at 0.5 or 0.125 µM, a mix of A2M (1 µM) and sKL (0.125 µM) or no active compound ("Control[0]"). They were then infected in same medium with a clinical isolate of SARS-CoV-2 at an MOI of 0.001 (strain hCoV-19/France/OCC-IHAP- VIR12/2020). To assess the antiviral activity of both A2M and sKL compounds in Calu-3 cells, the cells were pre-treated for 24 hours with A2M and/or sKL. Due to the specificity of this cell line, a 48-hours incubation was performed after an infection with a MOI of 0.01. To determine the IC50 and IC90 inhibitory concentrations, a range of 7 concentrations of A2M was used in parallel of the untreated negative and Remdesevir positive controls. [00282] Twenty-four (Vero E6) or 48 (Calu-3) hours post-infection, supernatant was recovered and processed for RT-qPCR experiment on SARS-CoV-2 gene E using Taqman OneStep RT-qPCR with E_Sarbeco primers and probe (PMID:31992387) and following instructions of the QIAGEN QuantiNova Probe RT-PCR Kit. [00283] Cells treated with 0.5 μM of sKL showed a significantly decreased viral titer compared to the negative untreated control (p<0.001) and is similar to that of the positive Remdesivir control with a drop of more than 95% of viral RNA detected (FIG.32). Treatments with both 1 and 0.25 μM of A2M did not lead to a reduction of the viral replication (FIG.32). Cells treated with A2M at 1 μM and sKL at 0.25 μM compounds in combination showed a significant decrease of the viral titer (p<0.001) compared to the untreated condition (FIG.32). This decrease was lower than the one observed with 0.5 μM sKL (p<0.001) but corresponds to a drop of more than 75% of viral RNA detected (FIG.32). [00284] Treatment with more than 0.625 μM of A2M triggered a significant reduction of the viral replication relative to the untreated control (p<0.001) (FIG.33). This decrease was similar (p>0.05) and higher (p<0.05) to Remdesevir positive control for 2.5 μM and 5 μM, respectively. 0.48μM and 1.42μM were determined to be the IC50 and IC90 inhibitory concentrations, respectively. [00285] Immunofluorescence confirmed the antiviral activity of A2M on Calu-3 cells with a significant decrease of the percentage of infected cells for 5, 2.5 μM and 1.25 μM of A2M (p<0.001) but also highlighted an effect at 0.625 μM of A2M (p<0.01) which was not observed by RT-qPCR (FIG.34). Attorney Docket: 51771-0003WO1 Example 6: Anti-Viral Effect of A2M and/or sKL in human and primate epithelial cells [00286] To evaluate the effect of A2M and sKL on SARS-CoV-2 replication in human and primate epithelial cells, Vero e6 and Calu-3 cells were treated with 7 different concentrations of A2M, sKL, A2M and sKL, and WM for 48 hours at 37 °C, 5% CO2. MTT assay was performed at 48 hours. No toxicity was observed in VeroE6 and Calu-3 with different doses of A2M, sKL, and A2M and sKL. CC50 values were higher than the maximum dose of the compound used in the toxicity experiment. See Table 10. [00287] Table 10 CC50 Condition [00288] To evaluate the antiviral effect of A2M and/or sKL in Vero E6 cells, VeroE6 cells were treated for one hour with A2M, sKL, A2M and sKL, or remdesivir (RDV) before infection. They were then infected in same medium with SARS CoV-2 alpha or Delta strain (Stocks replicated in Vero) at an MOI of 0.05 or 0.001 for 1 hour. Media was removed and the cells were treated with different concentrations of compounds and incubated at 37 °C, 5% CO ₂ . Cell supernatants were collected for viral RNA extraction at 48h. Replicates for each treatment group were pooled for RT-PCR. Copy numbers of gene N1 were determined using Taqman One step RT-PCR with CDC RUO primers and probes. [00289] Viral RNA was suppressed (0.3-0.5 log10 suppression) in cells treated with A2M and sKL and infected at an MOI of 0.05 with the alpha variant (FIG.35). Virus suppression control RDV-1uM in VeroE6 was not sufficient for viral suppression. [00290] At MOI of 0.001, combined treatment with A2M and sKL or with sKL alone trended towards suppression of alpha variant RNA at 24 and 48 hours (FIG.36) and resulted in a Attorney Docket: 51771-0003WO1 statistically significant suppression of alpha variant RNA for treatment with A2M alone (FIG. 36). For delta variant, sKL treatment trended toward viral suppression (FIG.36). These data demonstrate that A2M may be more relevant in cells that express TMPRSS. [00291] To evaluate the antiviral effect of A2M and/or sKL in Calu-3 cells, Calu-3 cells were treated 1 hour before infection with A2M, sKL, IBZ (i.e., A2M and sKL), or RDV. They were then infected in same medium with SARS CoV-2 alpha or Delta strain (Stocks replicated in Calu-3 cells) at 0.01 or 0.001 MOI for 1 hour. Media was removed and cells were treated with different concentrations of compounds and incubated at 37 °C, 5% CO2. Cell supernatants were collected for viral RNA extraction at 24 hours. Log copies of gene N1 were determined using Taqman One step RT-PCR with CDC RUO primers and probes. All results are mean ±SD of three different replicates. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001 and ns means not significant using student’s t-test relative to SARS CoV-2 ALPHA or DELTA infected cells- No Tx. [00292] For MOI = 0.01, sKL alone and A2M in combination with sKL demonstrated significant (p<0.0001) suppression of SARS CoV2 alpha replication at 24 hours (FIG.37) and trended towards suppression at 48 hours (FIG.38). SARS CoV2 delta replication (MOI = 0.01) was suppressed at 48 hours by combined treatment with A2M and sKL (p<0.001) and by treatment with sKL alone (p<0.05) (FIG.40); no significant effect was observed at 24 hours. The combination of A2M and sKL provides an example of synergism as the individual elements failed to suppress significantly the degree of viral replication of the delta variant. [00293] No significant effect was observed at the MOI of 0.001 (data not shown). Example 7: Effect of A2M and sKL on SARS-CoV-2 PLpro [00294] This example assesses the ability of A2M and recombinant human sKL, alone or in combination, to inhibit the catalytic activity of SARS-CoV-2 (2019-nCoV) PLpro by enzymatic assay. [00295] In SARS-CoV-2, Nsp3 contains 1945 residues (~212 kDa). PLpro is a domain of Nsp3—a large multidomain protein that is an essential component of the RTC. The enzyme is located in Nsp3 between the SARS unique domain (SUD/HVR) and a nucleic acid-binding Attorney Docket: 51771-0003WO1 domain (NAB). It is highly conserved and found in all coronaviruses, often in two copies, denoted as PL1pro and PL2pro. This cysteine protease cleaves peptide bonds between Nsp1 and Nsp2, Nsp2 and Nsp3, and Nsp3 and Nsp4, liberating three proteins: Nsp1, Nsp2, and Nsp3. [00296] Briefly, a PLpro enzymatic assay testing the catalytic activity of PLpro using the fluorogenic peptide substrate in a prompt fluorescence assay format was used. In this assay, the PLpro ability to cleave a fluorogenic peptide substrate, N-terminal-Z-Arg-Leu-Arg-Gly-Gly- AMC-C-terminal (Z-RLRGG- fluorophore AMC), was measured. The compound efficiently reacts with SARS-CoV-2 (2019-nCoV) papain-like protease for 30min first, then mixed with PLpro for 60 min, testing the formation of fluorescence product. In the presence of an inhibitor, formation of fluorescence product is reduced. PLpro inhibitor PR619 (M2565) from AbMole was used as a control. [00297] Results [00298] The combined drug of A2M plus sKL inhibited the activity of PLpro (FIG.41 and FIG.42; Table 11 and Table 12). SKL alone did not inhibit the activity of PLpro. A2M alone showed inhibition at the highest dose. The combined effect of sKL and A2M combination was higher than when used individually at the highest dose. [00299] Table 11. IC50 data for FIG.41 Relative IC50 Attorney Docket: 51771-0003WO1 [00300] Table 12. IC50 data for FIG.42 Relative Compound ID Top Bottom Slope [00301] Materials and Methods [00302] HEPES pH 7.5 (H3375-100G) was from Sigma (Saint Louis, USA). Triton-X 100 (X100-100ML) was from Sigma (Saint Louis, USA). BSA (V900933-100G) was from Sigma (Saint Louis, USA). DTT (D1532) was from Thermo Scientific (Illinois, USA). A2M (SRP6314- 1MG) was from Sigma (Saint Louis, USA). SKL (5334-KL-025) was from R&D systems (Minneapolis, USA). PLpro/papain-like protease-His recombinant protein (aa 1564-1880) (40593-V07E) was from YEASEN (Shanghai, China). PLpro assay substrate Z-Arg-Leu-Arg- Gly-Gly-AMC (custom) was from Biochem (Shanghai, China). PLpro inhibitor PR619 (M2565) was from AbMole (Houston, USA). [00303] Protein preparation [00304] A2M was supplied lyophilized from Sigma (Saint Louis, USA). It was reconstituted in sterile water at 7.25mg/mL. Its storage concentration is 10μM. sKL was supplied at 0.51mg/mL. Its storage concentration is 4.64μM. Both proteins were serially diluted by assay buffer into 8 points, by 3-fold. [00305] PLpro enzymatic assay experimental conditions and operation protocol [00306] Prior to the start of the assay, test Protein and PR619 was threefold diluted for 8 points.4uL of test Protein, PR619 in assay buffer or assay buffer alone was added to the appropriate wells. Next, 3ul of PLP enzyme (8nM final concentration) in assay buffer at pH 7.5 was dispensed into each well of a 384-microtiter plate (3ul buffer was added to the low-value Attorney Docket: 51771-0003WO1 control well). The plates were then incubated for 30 minutes at room temperature. The assay was started by dispensing 3ul of PLP substrate (250uM final concentration) to each well. After 60 minutes of incubation at room temperature, fluorescence was read on a envision using fluorescein filters: excitation wavelength of 360nm and emission wavelength of 460nm (As shown in figure). Example 8: Effect of A2M and sKL on human ACE2:SARs-CoV-2 interaction [00307] This example assesses the ability of A2M and recombinant human sKL, alone or in combination, to inhibit SARS-CoV-2 spike receptor binding domain (RBD) with its receptor angiotensin-converting enzyme 2 (ACE2) by homogenous time resolved fluorescence (HTRF) assay. [00308] Briefly, the binding between recombinant spike RBD, biotinylated and recombinant hACE2-FC was detected by HTRF method. This assay involves a reaction step and a detection step. For the reaction step, ACE2 Fc was mixture with RBD-His Biotinylated to start the reaction. For the detection step, the PAb Anti Human IgG-Eu Cryptate was labeled with Eu3 ⁺ -Cryptate, which can recognize the FC tag. When the streptavidin-d2 combines with the biotin, the FRET signal is detected. In the present of inhibitor, the FRET signal indicated by 665nm/615nm ratio is reduced. [00309] More specifically, prior to the start of the assay, test protein and ACE-his was threefold diluted for 8 points.2.5uL of test protein, ACE-his in assay buffer or assay buffer alone was added to the appropriate wells. Next, 2.5ul of ACE-FC enzyme (10nM final concentration) in assay buffer at pH 7.4 was dispensed into each well of a 384-microtiter plate (2.5ul buffer was added to the low-value control well). The plates were then incubated for 30 minutes at room temperature. The assay was started by dispensing 2.5 ul of RBD-His Biotinylated (50nM final concentration) to each well. The plates were then incubated for 60 minutes at room temperature, then add 2.5 ul of Detection Mix (with PAb Anti Human IgG-Eu Cryptate and Streptavidin-d2 in assay buffer) to each well. After 60 minutes of incubation at room temperature, read on envision in HTEF mode (excitation at 320 or 340 nm & emission at 665 nm) or measure the FRET signal (end point) in Envision instrument (HTRF 665/615 ratio is calculated from 665nm emission and 615nm emission) Attorney Docket: 51771-0003WO1 [00310] A2M alone, and combined drug of A2M plus sKL inhibited RBD’s binding with ACE significantly; SKL alone did not affect RBD’s binding with ACE (FIG.43 and FIG.44, Table 13 and Table 14). SKL showed a flat concentration dependent curve, the top is around 0%, bottom is around the 0% with no Relative IC50. A2M alone inhibited the binding of RBD with ACE in a concentration dependent manner. The highest level of inhibition was around 70%, the lowest being around 0%, Relative IC50 were 0.17uM and 0.079uM respectively in two runs. Combined drug (A2M plus SKL) inhibited the binding of RBD with ACE dose dependently. The maximum was around 80%, lowest was around 0%, Relative IC50 were 0.23uM and 0.086uM respectively in two runs. [00311] Table 13. IC50 data for FIG.43 Relative IC50 Compound ID Top Bottom Slope [00312] Table 14. IC50 data for FIG.44 Relative Attorney Docket: 51771-0003WO1 [00313] A2M alone, and combined drug of A2M plus sKL inhibited RBD’s binding with ACE. The combined drugs showed slightly higher max inhibitory efficacy than A2M alone, but the potency of combined drugs was slightly lower than A2M alone. [00314] Given that A2M and sKL inhibited SARS-CoV-2 spike RBD binding to ACE2, it was next determined whether A2M and sKL, alone or in combination, on the activity of SARS- CoV-2 pseudo virus infect cell line by pseudo virus entry assay. Briefly, pseudo virus used the lentiviral packaging system to package the SARS-CoV-2 S protein as a surface capsid glycoprotein and containing Luciferase dual reporter genes as a pseudo virus model. The pseudo virus can infect CaCo2 cells, which express the ACE2 gene. A pseudo virus entry assay testing the activity of pseudo virus to infect cell line was used. The infection efficiency was determined by detecting the value of Luciferase. A2M and sKL, alone or in combination, had no activity on pseudo virus entry assay (data not shown). [00315] Without being bound by any particular theory, these data suggest that the ACE2/A2m effect demonstrated in this example is likely due to steric inhibition. Example 9: Effect of A2M and sKL on cathepsin L [00316] Cathepsin L is a lysosomal cysteine protease. Enveloped viruses such as coronaviruses (e.g., SARS-CoV and MERs-CoV), ebolaviruses, hepatitis E virus, and Nipah virus require cathepsin L for their glycoprotein processing and cleavage. [00317] This example assesses the ability of A2M and recombinant human sKL, alone or in combination, to inhibit the catalytic activity of cathepsin L using the Cathepsin L Inhibitor Screening Assay Kit was from BPS Bioscience (San Diego, USA). E64, a cathepsin L inhibitor, was used as a control. [00318] The results are depicted in FIG.45 and Table 15 below. A2M and sKL inhibited the activity of Cathepsin L. sKL alone had little effect on the activity of Cathepsin L. A2M alone had the strongest inhibition. At the highest dose, the effect of sKL and A2M in combination was lower than that of A2M alone. Attorney Docket: 51771-0003WO1 [00319] Table 15. IC50 data for FIG.45 Relative IC50 Compound ID Top Bottom Slope Example 10: Protein:Protein Interaction Studies [00320] This example assesses the binding affinity of the interactions of SARS-CoV-2, ACE2, A2M, sKL, and CD147. [00321] Briefly, the protein targets were amine-coupled onto a CM5 Chip, and a series of concentration of partner proteins were prepared and injected to measure their affinity for the proteins (dilution ratio: 2; concentration levels: at least 5 (excluding curves with irregularities, abnormities, or high background)). All data were double referenced prior to fitting in Biacore Insight Evaluation Software v3.0, Cytiva to determine apparent KD. [00322] Surprisingly, despite the enhanced effect observed when sKL and A2M are combined (see, e.g., Examples 5 and 7), sKL had no measurable binding to A2M. Additionally, surprisingly despite the ability of A2M to inhibit SARS-CoV-2 spike RBD:ACE2 (see Example 8), there was no measurable binding of neither ACE2 nor SARS-CoV-2 spike RBD to A2M. Finally, there was no measurable binding of CD147 to A2M. Measurable binding between ACE2 and SARS-CoV-2 spike RBD was observed. Example 11: Effect of A2M and sKL on SARs-CoV-23CL Protease Attorney Docket: 51771-0003WO1 [00323] This example assesses the effect of A2M and recombinant human sKL, alone or in combination, on 3CL Mpro-mediated peptide cleavage activity. [00324] During coronavirus replication the large open reading frame (ORF) 1a/1ab genes, located at the 5’ end of the genome, are responsible for expressing two large replicase polyproteins (pp). These are co- or post-translationally cleaved by the virally encoded 3CLpro and Papain-like protease to yield 16 non-structural proteins responsible for viral replication. The 3CLpro is also termed the main protease as it cleaves a total of 11 cleavage sites within pp1a and pp1ab, in comparison to only three cleavage sites predicted for the papain-like protease. The 3CLpro has three distinct domains. The 3CLpro is so named for its close structural and sequence homology to the 3 chymotrypsin protease (3Cpro) of rhinoviruses, which contains a catalytic triad composed of His, Cys and Glu or Asp. Superimposition of the structures of 3CLpro and 3Cpro shows that the His and Cys of both proteases is almost perfectly aligned, which may explain the similar substrate specificity and catalytic mechanism. All coronavirus 3CLpro share a high sequence homology, as well as main chain architecture and substrate conservation. [00325] An 3CL Mpro enzymatic assay based on fluorescence resonance energy transfer (FRET) method was used. In this assay, there are two fluorophores that form a quenching pair and exhibit FRET within the 3CL Mpro substrate peptide. When the peptide is cleaved by the 3CL Mpro, the FRET disappears and the fluorescence increases. By monitoring the increase of the fluorescence, the enzyme activity can be detected at sub-nanomolar protein concentration with sufficient sensitivity. In the presence of an inhibitor, formation of fluorescence product is reduced which identified compounds that inhibit SARS-CoV23CL Mpro-mediated peptide cleavage activity. [00326] sKL did not inhibit the activity of 3CL Mpro (FIG.46). sKL showed a flat concentration dependent curve, the top is around 0%, the bottom is around 0%, relative IC50 could not be calculated (FIG.46). Surprisingly, A2M elevated the hydrolysis of the substrate peptide dose dependently (by 6-fold over baseline), showed a dropdown trend concentration dependent curve; the top is below 0% at the highest concentration, the bottom is around 0% and Relative IC50 could not be calculated (FIG.46). These data indicate that A2M cleaves the substrates directly. As with A2M alone, combination of A2M and sKL elevated the hydrolysis of the substrate dose dependently, showed a dropdown trend concentration dependent curve, the Attorney Docket: 51771-0003WO1 top is below 0% at the highest concentration, the bottom is around 0% and Relative IC50 could not be calculated (FIG.46). IC50 data is presented in Table 16, below. [00327] Table 16. IC50 summary. Relative Compound ID Top Bottom Slope IC50 [00328] In summary, sKL and A2M, alone or in combination did not inhibit SARS-CoV2 3CL Mpro-mediated peptide cleavage activity. sKL alone did not inhibit the activity of 3CL Mpro. However, A2M alone, and the combination of A2M and sKL, elevated the hydrolysis of the substrate peptide in a concentration dependent manner. These data indicate that A2M prematurely hydrolyses the virus during its maturation phase, thereby preventing lengthening of the RNA strand and rendering the particles functionally inert. Example 12: Effect of A2M and sKL on Vaccinia Virus Infection [00329] This example assesses the effect of A2M and recombinant human sKL, alone or in combination, on vaccinia virus. [00330] Briefly, HeLa cells were grown in DMEM without phenol red, supplemented with 10% FBS, 1mM sodium pyruvate, L-glutamine, and penicillin-streptomycin. Cells were plated in 96-well plates. [00331] For single dosing, cells were pre-treated with A2M, sKL, or A2M in combination with sKL 24-hours after seeding. Cells were incubated at 37 °C and 5% CO2 for 24 hours. 24-hours post pre-treatment, cells were infected with vaccinia virus-ANCHOR at MOI=0.05. Forty-eight hours post infection cells were fixed. [00332] For double dosing, cells were pre-treated with A2M, sKL, or A2M in combination with sKL 24-hours after seeding and incubated at 37 °C and 5% CO2 for 24 hours. 24-hours post Attorney Docket: 51771-0003WO1 pre-treatment, cells were infected with vaccinia virus-ANCHOR at MOI=0.05. Cells were treated with a second dose of A2M, sKL or A2M in combination with sKL 18 hours post infection. Cells were fixed 48 hours after infection. [00333] For positive control, an acyclonucleoside phosphonate having broad spectrum antiviral activity against poxviruses was used (referred to as “LAVR-289”). LAVR-289 is used at 1 µM to completely abolish replication. [00334] For cell fixing, cells were treated with 4% formalin for 10 minutes at room temperature, washed with PBS, and incubated with PBS Hoechst. [00335] Plates were imaged using a Thermo Scientific CellInsight CX7 HCS microscope. A compartmental analysis coupled with a spot detector algorithm was used to detect and quantify the infection rate (number of fluorescent cells over total number of cells). [00336] The infection rate reached 46% in non-treated control HeLa cells 48 hours post infection, in the one-dose treatment assay. For the single dosing, cells treated with A2M at 2 and 1μM showed a reduced infection rate compared to non-treated condition (FIG.47). sKL alone did not display a strong antiviral effect in VacV infection for the single dosing, although a slight dose effect was visible (FIG.47). A base concentration of 1μM of A2M in combination with low concentrations of sKL showed a synergic effect of both compounds on infection rate and lowered the infection rate by almost 50% in the three tested conditions (FIG.47). No specific effect on replication rate was observed in treated cells (FIG.48). [00337] In the double dosing treatment assay, the infection rate in non-treated cells was 35% at 48 hours post infection. This lower rate, compared to one-dose assay, was due to the removal of the supernatant, which contains viruses produced during the first hours of infection, when treating cells with second dose of A2M and/or sKL. Cells treated with A2M at 2 and 1 μM showed a reduced infection rate compared to non-treated condition (FIG.49). sKL alone did not display an antiviral effect in vaccinia virus infection (FIG.49). The combination of sKL and A2M lowered the infection rate at the 2 highest tested concentrations (FIG.49). Replication rate was not affected (FIG.50). [00338] In summary, in HeLa cells infected by vaccinia virus, A2M displayed a good antiviral activity and synergy was observed for the combination of sKL and A2M. Attorney Docket: 51771-0003WO1 Example 13: Effect of A2M and sKL on LPS-Induced Lung Inflammation [00339] This example assesses the effect of A2M and sKL, alone or in combination, on LPS-induced lung inflammation. [00340] Fifty female C57BL/6 mice, aged 6-8 weeks, were acclimatized prior to the treatment. All the mice were divided into 5 groups based on body weight: Control group (Group 1); Model (LPS) group (Group 2); LPS + TA1 (A2M and sKL) group (Group 3); LPS + TA2 (A2M) group (Group 4); LPS + TA3 (sKL) group (Group 5). All but the control group mice were challenged intraperitoneally with LPS injections of 1 mg/kg in 0.05 mL deionized water. Each mouse received intraperitoneal administration of 100 μL deionized water or test articles 0.5 hour before LPS injection. Serum and bronchoalveolar lavage fluid (BALF) were collected 4 hours after LPS injection from each mouse. Serum was assayed for murine cytokines (IL-1β, IL- 4, IL-6, IL-10 and TNF-α) by ELISA. BALF was analyzed for lymphocytes, microphage neutrophils, and eosinophils. [00341] The levels of inflammatory factors in serum of mice were shown in FIGs.51-55. Compared with the model group (Group 2), test articles groups (Groups 3-5) slightly inhibited IL-1β level in the serum of mice, but there was no statistical difference (P > 0.05). The percentage drop for IL-1β in the FIG.52 was 33 % (A2M and sKL), 11 % (A2M), 28 % (sKL), indicating that combined drug therapy (A2M and sKL) had a better therapeutic effect in IL-1β inhibition. The level of IL-10 in mice of Group 4 notably reduced compared with that of Group 2, and there is also a downward trend in Group 3 and Group 5. Analysis of IL-6 and TNF-α level indicated no obvious differences. [00342] The data of BALF cells count and cell percentage were shown in FIGs.55 and 56. Compared with normal group, lymphocytes and neutrophils in BALF increased significantly after LPS injection in Groups 2-5. Mice dosed by test articles (A2M or sKL) had less lymphocytes and neutrophils in BALF than model group, and combined drug therapy (A2M and sKL) was remarkable in inhibition of lung inflammation compared with model group. [00343] Conclusion: LPS (1 mg/kg) successfully induced an acute lung inflammation model in C57BL/6 mice. Compared with model group (Group 2), test articles groups (Groups 3- 5) reduced the levels of IL-1β and IL-10, and combined drug therapy (A2M and sKL) was good. Lymphocytes and neutrophils in BALF in Groups 3-5 were decreased compared with model Attorney Docket: 51771-0003WO1 group. In conclusion, combined treatment with A2M and sKL had a good inhibitory effect on LPS induced lung inflammation model in mice. Example 14: Effect of A2M and sKL on Skin Tissue: Inflammation [00344] This example assesses the effect of A2M and sKL on inflammation in human skin tissue. The test was carried out on skin explants. Full-thickness skin biopsies were embedded in a solid and nourishing matrix while the epidermal surfaces were left in contact with air. The skin biopsies were firmly embedded in a matrix, preventing any lateral diffusion of topically applied formulations. The following donors were used: Donor 1: woman, abdominoplasty, 50 years old, phototype 3; and Donor 2: woman, abdominoplasty, 63 years old, phototype 3. Testing was performed in triplicate. Skin explants were either untreated or treated with 0.5 µM sKL (Bio- Techne, Catalog No.5334.KL.025; amino acids 34-981) combined with 1 µM A2M (Sigma- Aldrich, Cat. No SRP6314-1). The skin explants were treated by systemic application (sKL and A2M proteins in the culture medium) for 7 days. The culture media was changed every 2 days with fresh proteins. Supernatant was collected at day 7 (D7) and used to perform the evaluate inflammation markers. [00345] Collected supernatants were put in contact with beads of different size and internal fluorescence intensity. Beads were conjugated with specific antibody targeting inflammation mediators. These beads were differentiated by their size and internal fluorescence intensity by flow cytometry (MACSQuant® Analyzer 10 Flow Cyrtometer – Miltenyi Biotec) allowing to separate specific cytokine populations and quantify them. The mean of the concentrations of the different cytokines was quantified and the mean values were compared to the untreated control to express an activating or inhibiting effect (Table 17). To compare the means, a Statistical Student test or Mann-Whitney test was used with GraphPad Prism Software® (ns>0.05, *<0.05, **<0.01, ***<0.001 and ****<0.0001). Results are provided in Table 17. [00346] Table 17. Summary of Results. Data presented as the percent change in mean concentration of the indicated marker relative to untreated control for each donor individually (Donor 1, Donor 2) or for the two donors combined (Global). Attorney Docket: 51771-0003WO1 Donor 1 Donor 2 Global (concentration %) (concentration %) (concentration %) * * [00347] On Donor 1, the sKL and A2M treatment caused a significant increase in IL-18 concentration (+47%) (Table 17). On Donor 2, the sKL and A2M treatment significantly increased IL-1β (+110%), IL-10 (+43%), and IL-18 (+44%) and decreased IFN-α2 (-15%) (Table 17). The treatment had a greater impact on Donor 2 than on Donor 1 (Table 17). By pooling the results obtained on the two donors, the sKL and A2M treatment resulted in concentration changes for IL-1β (+57%), IL-10 (+31%) and IL-18 (+45%) (Table 17). In summary, treatment of skin biopsies with sKL and A2M significantly modulated the following cytokines: IL-1β, IFN-α2, IL-10 and IL-18. Example 15: Effect of A2M and sKL on Skin Tissue: Protein Expression [00348] This example evaluates the effect of sKL and A2M on markers implicated in DNA double-strand breaks and extracellular matrix composition in skin tissue. [00349] The evaluation was carried out on skin explants. Full-thickness skin biopsies were embedded in a solid and nourishing matrix while the epidermal surfaces were left in contact with air. The skin biopsies were firmly embedded in a matrix, preventing any lateral diffusion of topically applied formulations. The following donors were used: Donor 1: woman, abdominoplasty, 50 years old, phototype 3; and Donor 2: woman, abdominoplasty, 63 years old, Attorney Docket: 51771-0003WO1 phototype 3. Testing was performed in triplicate. Skin explants were either untreated or treated with 0.5 µM sKL (Bio-Techne, Catalog No.5334.KL.025; amino acids 34-981) combined with 1 µM A2M (Sigma-Aldrich, Cat. No SRP6314-1). The skin explants were treated by systemic application (sKL and A2M proteins in the culture medium) for 7 days. The culture media was changed every 2 days with fresh proteins. [00350] Following treatments, explants were fixed with formalin, embedded in paraffin, and sectioned for labelling. Biomarkers of interest were specifically detected by immunofluorescence and the nuclei were labelled with DAPI. The labelling was observed under a Zeiss Axio Green fluorescence microscope. The measured fluorescence was quantified relatively by Image analysis (Image J). The mean of the fluorescence intensities + standard error of the mean (SEM) was plotted. The values were related to the untreated control (100%) for the compilation of donor. A statistical Student or Mann Whitney test (depending to Gaussian repartition) was carried out on data using GraphPad Prism Software® (ns>0.05, *<0.05, **<0.001 and ***<0.0001). [00351] In skins exposed to A2M and sKL, a disruption of epidermis in some areas was observed, despite a systemic treatment (data not shown). Despite this, there was low toxicity. [00352] Analysis of γH2Ax expression [00353] Phosphorylation of the Ser-139 residue of the histone variant H2AX, forming γH2AX, is an early cellular response to the induction of DNA double-strand breaks (J. Mah et al., 2010). The γH2AX labelling increased in nuclei of samples treated with sKL and A2M compared to untreated ones (+2.7%***) (Table 18); however, this level remained very low. [00354] Analysis of Collagen I expression [00355] Type I collagen is present in skin, tendon, vasculature, organs and bone. The activities of the enzymes required to synthesize collagen fibres have been reported to vary with age. The proportion of the collagen types in skin change with age. Young skin is composed of 80% type I collagen and about 15% collagen type III. With age, the ability to replenish collagen naturally decreases by about 1.0%-1.5% per year (Reilly and Lozano, 2020). The Collagen I expression significantly increased after treatment with sKL and A2M compared to untreated samples (+66.1%***) (Table 18). Attorney Docket: 51771-0003WO1 [00356] Analysis of Collagen III Expression [00357] Type III collagen is commonly found alongside Type I and usually represents about 15% of skin collagen (Reilly and Lozano, 2020). On the two donors, the Collagen III expression was similar between both untreated and treated conditions (Table 18). [00358] Analysis of Collagen IV expression [00359] Type IV collagen is a major component of skin basement membrane. Certain results suggest that type IV collagen decrease with aging involves a TGFβ signaling pathway (Feru et al., 2016). The Collagen IV expression decreased slightly—but not significantly—with sKL/A2M treatment compared to untreated samples (Table 18). [00360] Table 18. Data presented as the percent change mean fluorescence intensity of the indicated marker relative to untreated control. Bold = positive effect; italics = negative effect; all others = similar, not significant. Donor 1 Donor 2 All Donors Example 16: Effect of A2M and sKL on Gene Expression in Human Skin Cells [00361] This example assesses the effect of sKL (Bio-Techne, Catalog No.5334.KL.025; amino acids 34-981) and A2M (Sigma-Aldrich, Cat. No SRP6314-1) on gene expression in human skin cells. Tests were performed on Normal Human Dermal Fibroblasts (NHDF, 68 years old, woman). [00362] The conditions tested were: (i) NHDF untreated; (ii) NHDF + sKL 0.05μM 48 hours; (iii) NHDF + sKL 0.025μM 48 hours; (iv) NHDF + A2M 0.5μM 48 hours; (v) NHDF + A2M 0.25μM 48 hours; (vi) NHDF + sKL /A2M 0.05μM/0.5μM 48 hours; and (vii) NHDF + sKL / A2M 0.025μM/0.25μM 48 hours. This first group of conditions was composed of NHDF Attorney Docket: 51771-0003WO1 with one population doubling. These cells were seeded at a concentration of 10,000 cells per well in 96-well plate in the presence of suitable culture media (Promocell). After adhesion (one day), the tested proteins at the chosen concentration were added for 48 hours. [00363] The second group of conditions were: (i) Replicated NHDF untreated; (ii) Replicated NHDF + sKL 0.05μM 48 hours; (iii) Replicated NHDF + sKL 0.025μM 48 hours; (iv) Replicated NHDF + A2M 0.5μM 48 hours; (v) Replicated NHDF + A2M 0.25μM 48 hours; (vi) Replicated NHDF + sKL / A2M 0.05/0.5μM 48 hours; and (vii) Replicated NHDF + sKL / A2M 0.025/0.25μM 48 hours. This second group of conditions was composed of NHDF, with 12 population doublings (8 weeks of cell culture). These cells were grown in 12-well plates with appropriate medium. After this replication phase, they were seeded at a concentration of 10,000 cells per well in 96-well plate in the presence of suitable culture media (Promocell) After adhesion (one day), the tested proteins at the chosen concentration were added for 48 hours. [00364] The third group of conditions were: (i) Replicated NHDF + sKL 0.05μM; (ii) Replicated NHDF + sKL 0.025; (iii) Replicated NHDF + A2M 0.5μM; (iv) Replicated NHDF + A2M 0.25μM; (v) Replicated NHDF + sKL / A2M 0.05/0.5μM; and (vi) Replicated NHDF + sKL / A2M 0.025/0.25μM. This third group of conditions was composed of NHDF with 12 population doublings (8 weeks of cell culture) and that were exposed to the test proteins during all the phase of replication. The treatments with the tested proteins was changed twice a week. The cells were grown in 12-well plates with appropriate medium. After the replication phase, they were seeded at a concentration of 10,000 cells per well in 96-well plate in the presence of suitable culture media (Promocell) After adhesion (one day), the tested proteins at the chosen concentration were added for 48 hours. [00365] For each study, sKL was obtained from Bio-Techne (Catalog No.5334.KL.025; amino acids 34-981) and A2M was obtained from Sigma-Aldrich (Cat. No SRP6314-1). [00366] The mRNAs were extracted, and the reverse transcription performed. Finally, the specific preparation steps for the chip according to the Fluidigm protocol were undertaken. [00367] A pre-amplification step in the presence of all the primers used on the chip is carried out. Each pre-amplified cDNA sample is then placed in a 96-well plate according to the plate plan with the mix allowing real-time PCR. In parallel on another 96-well plate, each pair of primers is placed in one well according to the plate plane. Then each mix is deposited on both Attorney Docket: 51771-0003WO1 sides of the chip. The two mixes are mixed by the IFC Controller and then the chip is placed in the BioMark®-Fluidigm to perform real-time PCR. [00368] The specificity of each primer pair was checked for all cell conditions by analyzing the dissociation curves and the problematic points with double peaks were removed from the analysis. Each CT was then normalized by the reference genes and compared to cell control condition, here the cells with one population doubling or 12 populations doubling, to calculate the ΔΔCT. Then the relative expression was calculated using the formula 2-ΔΔCT. For each condition, the standard error of the mean (SEM) was calculated and the points with oversized SEM (if the SEM is > 40% of the mean of the 3 values) were removed from the analysis. The genes were then classified by cell type to eliminate data not corresponding to the cell models. The results are expressed in percentage of over-expression or under-expression with respect to the reference condition. [00369] The results are represented in Table 19. Represented in Table 19 are the percentages of activation and inhibition in relation to the basal level. The changes in gene expression greater than 50% induction and greater than 40% inhibition are presented.

₁ O ^W _{n 3} ^{o 0} _{i 0} ^t % ⁰ _a ⁰ ₂ ^% % ⁰ % ⁰ - ⁴ % ⁰ _{0 9 0} ^%% ₀ ^% ₀ ¹ _r ^o m ^{%% %% e} _{0 0 0 0 + 1} ^{1 6} ₂ ⁴ ₇ ⁴ _{+ 0} ^{6 4} ₈ ⁸ _{4 7} ⁷ ₁ ⁵ _v ^it : _{i t} ^{s e} _{o k} ^{p c} _o ^{y D} _ll ^{y a} _{e b} ⁿ _r ^o _l ^{o g t} _t ^y t A _i ^v _i ^t _c ^{a = β} _; ^y t _i ^v _i ^t _c ^a _l ^a _i ^ci _f ^e _n ^e _{b = α} ^; _sl ^l _e ^{c d} _e ^t _a ^c _i ^l _p ^e _r ⁿ _{u n} ^{o M} ₂ A d ⁿ _a L _a K ^{r s} _{e r f} ^{v a} _l ^{d u} _n ^% ₀ ^{% %} l _x ^a _e ^{r 6 %} ₀ ⁴ ₀ ^{4 o} _o t ₌ ^l _e ⁱ _r ^{t si} _{s u} ^t _{+ 0} % c ₁ ^{0 0} - _{5 1} ^% - _{0 1} ^% _{0 c} ^{e δ C} f ^f _{; a} s ^r _a ^{e u} A _{1 t} M _h ^t _r ^{t 1 + +} A ⁷ L N ⁵ - A ^{5 8} - _e ^{i x} _{n s E} ^y _s ^O C _β ^G M _L ^T B ^U _{L β} ^O C _{P L} O ^T _{P E} t D _{γ C} D _{γ . i 1 t} a ^v i ^t a e 0 _{[ d 1} O ^W _{n 3} ^{o 0} _{i 0} ^t % ^{0 %} % % ^{0 0} _{a 0} % ⁰ ₄ ^%% m _{0 0 0 0} - ¹ ₇ m ⁷ ₁ ^{al 5} _f ⁿ : _{I t} ^e _k ^c _o ^{t D} _n ^{a y} _e ^g _d ⁿ _n ⁱ _r ⁱ _x ^o _g ^{o t} _t ^a _i - ^t i ^t _n A A _n ^a e ^v i _t ⁿ _e ^v _, ^l e _a ^{h r v} _{i t P} ^v _r ^{w u} _{o S} ^r _{g g} ⁿ _i ^z _i ^r _u ^t _s ⁱ _o M r ^a _l ^u _{0 l} ^l _x ^{i 0} r ₁ g _{e n} ^{t i C} _{a g a} a ^r _t M - _i ^{t x} n _E a e ^v _i ^t _{a n} r ^o u _i ^s C _e ^h _d A r ^a _l ^u _l ^l _{x e} ^{i C} _r ^t a ^r _{a t} M x E Attorney Docket: 51771-0003WO1 [00371] The following are genes whose expression was affected by the treatments applied in “unreplicated cells” (Table 19): CDC42, CTNNA1, LAMA5, COL17A1, COL7A1, HMOX1, MGST1, SOD2, BCL2, AQP1, MMP1, MMP3, BGN, COL5A1, HAS2, SDC4, DPT, LUM, COX2, FST, IL6, IL8, BSG, INSR, SIRT2, SIRT3, SIRT4, SIRT6, and HBEGF. A rather beneficial effect of sKL, which shows a decrease in inflammation genes and an activation of antioxidant defenses and certain key markers of the dermis, was observed. The addition of the A2M protein (with or without sKL) had a drastic effect on gene expression. Extremely surprisingly, the addition of the protein strongly activates the inflammation genes: mediator and proteases. With A2M, the activation of the SOD2 gene was observed. The antioxidant defenses genes were also activated by A2M as well as the genes involved in skin hydration. [00372] The effect of replication is provided in Table 20. Only the effect of successive reapplications on gene expression was observed. The following are genes whose expression was affected by the treatments applied (Table 20): CD44, CDC42, CTNNA1, FN1, COL4A1, COL7A1, GLRX, HMOX1, MSRA, MSRB2, NRF2, PPIA, BAX, BCL2, SDC1, AQP1, ATP5A1, GLS, MMP1, TIMP1, BGN, COL1A1, COL3A1, COL5A1, DCN, FBN1, FBN2, HAS2, VCAN, DPT, LOX, LUM, P4HA1, PLOD3, SPARC, COX2, IL6, IL8, FST, TGFB1, TNFA, BSG, INSR, SIRT1, SIRT4, SIRT5, SIRT6, SIRT7, SIRT3, and HBEGF. [00373] The replications had a huge effect on gene expression that was not consistent with the literature. Indeed, almost all the genes tested involved in the formation and structure of the dermis were activated. This was also the case for all the genes involved in cell renewal and energy metabolism. Normally these activities are reduced in replication-aged cells. Here, already aged donors were replicated.

₁ O ^{m % W} ₃ ^{y 0} _{g si} ^l _{0 0 o} ⁸ ₊ ^% ₀ ⁰ - ¹ _e ^r ₇ ^v _e i ^{n b} _{a 1} ^{2 t A} _{5 5} ^{+ 7} _{t Ee 1} ^{a 5} _g m ^P _T ^S A _L G _α : ^e _t ^e _{n k} ^c _{y o} ^{b D d y} _{e e} ^{y n} _{a r} ^{l o} _e ^t _t ^d _r A ^{o e} _v ^it _i ^s _o ^{p y} _ll ^a _b ^o _l ^{g yt} _i ^v _i ^t _c ^{a = β} _; ^yt _i ^v _i ^t _c ^a _l ^a _i ^c i _f ^e n ^{c e} i _{f o P} Q _S A b ^e M n A H _{α =} ^e α _b ;s _{y r l} ^{l b a} _l ^u e ^d _l ^l _{x n} ^{% c} _{e e} ⁱ _r ^o i ₀ ^{% t} _t ^{1 c} _{3 0} ⁴ - d ^y e _a ^{g C} _a ^r _{a e} ^{t +} o ¹ _P ¹ _P t ^l a _{e n} c ^{d i} _{g t} M x ^{r i} _{E p} MM ^I l _r ^{a o} _-i ^t M _{T γ} p _e ^{r y} _{n t} ^a f _i ^v _e ^v _{i n} ^{% o} _{i 0} ⁷ % ⁰ % ^{0 o} _i t _{t c} ^{c t e} _{a a n} r ^o _i ^s % s _e ⁰ _{2 1 7} ^{1 %} _{0 e} ^{h %} ₅ ^{1 4} ₊ ³ _{+ +} % ⁸ _{+ f} ^f _{e u E} ^v _i C ^h _{o d} C ₀ ⁴ _{+ 1 1 1} ⁰ _{7 5 d - 2} ⁴ A ⁴ A ⁷ A N ⁶ ₊ A . ^t _a A ^{n 4} a ₄ D _C D _L O _L N ₁ M 0 ^g _{e C C} ^OTNA 2 _e ⁿ _{C C C F L β} l _{l b} ^{l a} _a ^r T _{e r} ^s i v ^a _{l s} ^e _e ^% ₀ %% o ^u _{l =} ^l _h ^r _u % ⁷ ₁ ⁰ ₆ ⁰ ₂ ^{% %} ₀ ^% e ^t _n ^t _c ^{u 0} ₈ ² ₊ ² ₊ ⁹ % _{0 +} ^{0 1 %} ₀ ^% ₀ ^% ₀ ^% ₀ ^{6 7} _{5 0} ^{5 δ Cy} ; _{a s x r} ^t _s ⁶ _{3 1 1 1} ^% ₀ ^% ₁ 7 ₀ ² _{8 +} ⁹ ₊ ² ₁ ⁴ ₇ ⁸ _{+ +} ⁺ ₃ ^{+ s r} _t ^{i x} _r ^t _d ⁺ A N ¹ AA - ⁸ L ³ _L ⁵ _L ^N - _{1 2} ^{+ +} _{1 3} AD ^C RN ] ⁴ _e ⁱ t _Ea ⁿ M _a ^G _B ^O _C ^O _C ^O _C ^T _P N BNXM B ^OU H ⁴ O ^L A ^{A P} _{C 7} ³ _i ^v _C D D _{F F L L P P S} V _β 0 [ ^c a Attorney Docket: 51771-0003WO1 [00375] The effect of sKL and/or A2M on replicated cells at 48 hours or during the replication is provided in Table 21. The following are genes whose expression was affected by the treatments applied (Table 21): CD44, CDC42, CTNNA1, FN1, COL4A1, COL7A1, CAT, GLRX, HMOX1, MSRA, MSRB2, NRF2, PRDX1, PPIA, BAX, BCL2, SDC1, AQP1, ATP5A1, GLS, MMP1, MMP3, TIMP1, BGN, COL1A1, COL3A1, COL5A1, DCN, FBN1, FBN2, HAS2, VCAN, DPT, LOX, LUM, LOXL1, P4HA1, PLOD3, SPARC, COX2, IL6, IL8, FST, TGFB1, TNFA, BSG, INSR, SIRT1, SIRT4, SIRT5, SIRT6, SIRT7, SIRT2, SIRT3, HBEGF, and TNC. The addition of sKL and/or A2M did not modify or only slightly modified the profile of cells aged by successive replication (Table 21). An increase in the expression of inflammation mediator genes induced by A2M was observed. Activation of the SOD2 gene was also observed. [00376] In summary, the beneficial effect of sKL was observed. Additionally, A2M showed a very strong effect—despite the concentrations used—and activated inflammation at the gene level. The results of the study could only be exploited on non-replicated cells. Indeed, the successive replications resulted in changes in the gene expression profile, which did not allow for detection of the effect of the products on replicative aging in a precise manner.

₁ O ^W ₃ ⁰ ₀ ^{y s} _i ^{l 0} - ⁼ _g ^r _o ^b ₁ A % ¹ ₇ ^β _{= e} ⁿ _a ⁷ _{; E} ^t m e ₅ ^{P %} ₀ ^{S 0} _{9 1} ^{y 5 t} _i ^{γ v} _; m _T A ⁶ _{+ L} G ³ _{+ α i} ^s : _t ^{e t} _{k c} ^c _o ^a _l ^{D a y} _{i e} ^c i ⁿ _{f r} ^{e ot} _{n t} ^e A _{b = α} ^; _n ^o _i ^t _a ^c _i ^l _p ^e _{r g} ⁿ _i ^r _u ^d _r ^o s ^r _u ^o _{h 8} ^4t _a s _l ^l _e c ^{v d} _{o e} ^t _{= a} ^{δ -} _{a r n} ^% ₀ r ^a _{l x} c _{i ;} ^{u i} _r ^oi _t ^{c 4} - l ^{s g} _t ^x _l ^{l t} _{a e} ^{t 1} _P % ¹ _{P p e} ^{i e} _{t n} ⁱ _Ee C M _o ^r M ⁰ ₈ M r _{i g p} M ⁴ ₊ ^I _{T γ n} ^{vi o} _t ^a - c _{i a} ^t _n ^a _n M _{e 2} ^v _e i ^v _{i n} ^{o o} _i ^s _e ^% % A _t r ^{a t} _{i o g a} ^{s r} _e ^{h e} _u ^h _{o 0} ⁴ ₁ % _{1 1} ⁰ A ₈ C _{- 2} ⁴ %A ^{4 0} ₃ A%N ⁵ ₊ C _{d d} ⁴ _{4 C} ⁰ _L ^{6 7} _L ⁰ N ^% _{1 L n} A ⁿ _a ^DD ₀ ^{1 O} ₂ ^{1 O} ₃ ^{3 T} ₀ ^{9 N} K _y s ^b _{C C + C + C + C + F β f} ^{d ot} _{e c} ^y _r e _{a f} ^{l a} _l ^d _n % e ⁰ % 6 ⁰ ₁ ^% % f _e ^u _l ^{% l} _x ^{i a} r ^{s r} % u ⁰ ₄ ² ₊ ⁸ % _{0 +} ^{0 5} % ^% ₀ ⁰ ₅ ^% ₀ % 6 ⁰ _{7 0} ⁷ E ^d _{r e} C ^t _a ⁱ _s ^{t e} _c ⁴ _{4 1 1 1} ^% ₀ ^% _{1 9 0} ² ₊ ⁷ ₊ ⁰ ₉ ² ₅ ¹ _{+ +} ⁶ ₃ ⁺ . ^o _a ^r _t M _h ^{t u} _r ^t _s ⁺ A ^{1 %} ₀ AA ^{7 1 3 5} - ⁹ - _{1 2} ^{+ +} _{1 3} AD ^C RN 1 ₂ ^e _v ^x _n N _{L E} ^y _{s e} ^{i GO} ₂ ² _L O _L O ^N C ^T _P N BNXM B ^OU H ⁴ O LA ^A C l ^t _i ^s _{B C + C C} D D _{F F L L P P} ^P _S V _β a T ^{p y} _. l ^yt b i ] ^g _a y _e i _i 0 0 _{t g [} ^c _a ^e _{n 1} O ^W ₃ ⁰ ₀ ⁰ - ¹ ₇ ⁷ ₁ ⁵ : _t ^e _k ^c _o ^{D y} _e ⁿ _r ^ot _t A g _n ⁱ _g ^a _-i ^t _n ^a e ^v i _t ⁿ _e ^v _e ^r _P g _n ⁱ _g ^a - _i ^t _n ^a e v _{i n i} ^s _{0 0} t ^o _{i a} ^s _e ^{h %} ₀ ⁶ % r _{e o} ⁴ _{+ 1} % ₁ ⁰ ₃ ^% ₀ % 1 % ₁ ⁰ ₈ ⁵ - ₅ ^% _{0 u} ^h C _{- 2} ⁴ A ^{4 0} ₀ A ⁷ % ⁴ ₊ ⁵ - A ^{4 0} ₄ A ⁷ % ⁴ ₊ A ⁴ - C _d ⁴ A _d ⁿ ₄ D _CL ^{3 O} _{0 L} ^{0 O} _{6 1} ⁴ ₄ D _L ^{4 O} _{0 L} ^{0 O} _{1 1} MN a _C ^D _{C C} ¹ _{+ C} ² ₊ ^N _{F β C C} ¹ _{+ C} ¹ ₊ ^N _F ^A _L ^X _{P β r} ^a _l ^d % %% u _{n l} ^l _{x e} ^{i a} _e ^{%0 s r} % _{0 1 u} ⁰ % ^% ₀ ^% 3 ⁹ ₁ ⁶ ₊ ^{0 4 %} ₀ ^% _{0 0} ^{6 %} 4 ₀ % ^{0 7 0} ₈ ⁰ ₃ ^% ₀ % 1 ¹ ₊ ⁵ ₊ ^{%3 %} ₀ ^{0 %} 1 ₀ ^{4 %} 4 ₀ ^{8 C} _{r a} ^t _a ⁱ _s ^{t e} _c ^{u 5} _{3 1} ^%% ₂ A ^% ₁ A ₁ A ₀ ⁸ ₀ ¹ _{6 +} ⁶ ₊ ¹ ₄ ⁹ _{+ 1} ⁺ ₂ ^{7 %%} ₀ C ⁺ _{2 1} % _{1 1 0} ⁷ ₀ ⁷ _{4 +} ⁴ ₊ ² ₄ ¹ ₊ ⁺ ₁ ^{+ r} _t M _h x ^t _{r n} ^t _s ⁺ N ¹ _L0 ^{9 3} _L ⁵ - ⁹ L - E ^y _s ^{G NT} ₁ N ₂ ⁺ N ⁺ A NMA _R ^A N ¹ _L0 A 0 ³ A L ⁵ - ⁹ L - ⁺ ₁ ^{C N} N T ₁ N ₂ NMA _R ^A B ^O _{7 C} ¹ ₊ ^O C ^O C _C D _P D ^B _F ^B _F ^U H L ⁴ A P ^P _{S C} V _β ^G B ^O _{0 C} ¹ ₊ ^O C ^O C _C D _P D ^B _F ^B _F ^U H L ⁴ A P ^P _{S C} V ₁ O ^W ₃ ⁰ ₀ ⁰ - ¹ ₇ ⁷ ₁ ⁵ : _t ^e _k ^c _o ^{D y} _e ⁿ _r ^ot _t A g _n ⁱ _g ^a _-i ^t _n ^a e ^v i _t ⁿ _e ^v _e ^r _P g _n ⁱ _g ^a - _i ^t _n a _{n e} ^v _{i n} ^o _i ^% ₀ t ^o _i ^s _e ^% a ^{s r} _e ^h _{o 0} ⁷ % 4 _{+ 1} % ₁ ⁰ ₄ ^% ₀ ⁵ _{1 1 1} % ⁰ A _{7 u} ^h - _d C ⁴ ₂ ⁴ A ^{4 0} ₃ A 2 ⁷ % ⁵ ₊ - 4 ₂ ⁴ %A ^{4 %} ₀ A ⁷ %N ⁶ ₊ C A _d ⁿ ₄ D _C D _L O _{2 L} ^{0 O} _{8 1 C C} ^{0 D} _{2 L} ^{8 O} _{6 L} ^{0 O} ₁ N ^% _{0 1 a C C C} ¹ _{+ C} ⁴ ₊ ^N _F ^D _{S β C} ¹ _{+ C} ⁶ _{+ C} ¹ ₊ ^T _C ⁹ ₊ ^N _{F α r} ^a _l ^d %% u _{n l} ^l _{x e} ^{i a} _e % ⁰ ₉ ⁰ % 7 ^% % ^{0 %} ₀ ^% % ⁰ % 3 ⁰ % 5 ⁰ ₄ ^% % ^{0 %} ₀ ^{% s r} _u ^{0 1} ₊ ⁶ % ⁰ ₀ ^{1 %} _{0 0} ⁰ ₀ ^{8 0 7 2 7} ₀ ^{1 %} _{0 5} ⁶ ₀ ^{3 C} _{r a} ^t _a ⁱ _s ^{t e} _{c 5} u ⁷ _{+ 4 1} ^%% _{3 3} ^{3 1} A ^% ₁ A _{1 0} ⁶ ₀ ¹ ₊ ⁶ _{+ 4 + 3} ⁺ ₂ ⁺ ₄ ¹ _{+ + + 4 1 1 1} ^% ₀ ^{6 %} _{1 0} ⁷ ₊ ² ₆ ¹ _{+ 5} ⁺ ₃ ^{+ r} _t M _h x ^t _{r n} ^t _s ⁺ N ¹ _L0 ¹ E ^y _s ^G ₉ ³ A L ⁵ - ⁹ L - N ^T ₁ ⁺ ₁ ^C N ⁺ A N ₂ NMA _R ¹ A ³ A ⁵ - ⁹ - ⁺ ₁ ^C N A ^A N _LLL ^NT ₂ NMA _R A ^A B ^O C ¹ ₊ ^O C ^O C _C D _P D ^B _F ^B _F ^U H L ⁴ _P ^P _{S C} V _β ^G B ^O C ^O C ^O C _C D _P D ^B _F ^U H L ⁴ _P ^P _{S C} V ₁ O ^W ₃ ⁰ ₀ ⁰ - ¹ ₇ ⁷ ₁ ⁵ : _t ^e _k ^c _o ^{D y} _e ⁿ _r ^ot _t A g _n ⁱ _g ^a _-i ^t _n ^a e ^v i _t ⁿ _e ^v _e ^r _P g _n ⁱ _g ^a - _i ^t _n a _{n e n} ^o _i ^% ₀ ^{% v} _i ^{t o} _i ^s a ^s _e ^{8 h} _{1 +} % r _{e 5} ⁰ ₉ ^% _{0 0} ⁵ % 5 _{+ 1} % _{1 1} ⁰ ₈ ^% 5 ₀ ⁶ u ^h _o C ₂ ⁴ A %N%A ⁺ C _d ¹ _{- 2} ⁴ A ^{4 0} ₁ A ⁷ A %N ⁵ ₊ A% - 1 A _d ⁿ _C ^{0 D} ₈ N ⁰ ₄ M _C ⁴ ₄ D _CL ^{9 O} _{4 L} ⁰ ₉ N ^% _{0 1} M ⁰ _{4 C a C} ² ₊ ^T _C ² ₊ ^A _L ^D _{S α C} ^D _{C C} ¹ ₊ ^O C ¹ ₊ ^T _C ⁹ ₊ ^N _F ^A _L ¹ ₊ ^D _{S β r} ^a _l ^{d u} _n % l ^l _{x e} ^{i a} _e % ⁰ %% 5 % ^% % ^{0 %} ₀ ^% % ⁰ ₃ ⁰ ₀ % ⁰ % ^{0 %} ₀ ^{% s r} _u ^{0 2} _{0 +} ^{0 7 %} _{0 8} ⁹ _{7 0} ^{3 0 2 7} % ⁰ ₉ ^{4 %} _{0 5} ⁴ ₀ ^{8 C} _{r a} ^t _a ⁱ _s ^{t e} _{c 9} u ⁰ _{0 2 1} A ₁ A ^%3 ₅ % + ³ ₊ ⁰ ₈ ¹ ₈ ² _{+ 1} ⁺ _{3 5} ⁸ _{+ +} ^%% _{1 0} ^{3 1 C +} _{4 1} A ^% _{1 1 0} ⁹ ₀ ¹ ₊ ¹ _{+ 2 + 8} ⁺ ₁ ^{+ r} _t M _h x ^t _{r n} ^{t + 3 5} _{0 1 2} ^{+ +} A E ^y _s N _LL ⁷ s ^G ₂ NNXM _R N ^{+ 1} ₀ A ³ A ⁵ - ⁹ - _{1 2} ⁺ ₁ ^C RN HA ^A B ^O C ^O C ¹ ₊ ^B _F ^B _F ^O _L ^U _L ⁴ _P ^P _{S C} N _L ¹ _{6 LL} ^N A V _α ^G B ^O C ¹ ₊ ^O C ^O C _C ^T NNMHA ^A D _P D ^B _F ^B _F ^U _L ⁴ _P ^P _{S C} V ₁ O ^W ₃ ⁰ ₀ ⁰ - ¹ ₇ ⁷ ₁ ⁵ : _t ^e _k ^c _o ^{D y} _e ⁿ _r ^ot _t A g _n ⁱ _g ^a _-i ^t _n ^a e ^v i _t ⁿ _e ^v _e ^r _P g _n ⁱ _g ^a - _i ^t _n a _{n e} ^{o v} _{i n} t ^o _{i i} ^s a ^s _e ^{% h %} ₀ % ₀ % ^{0 r} _e ⁴ _{1 1 1} ⁰ ₅ ^% ₀ ³ _{1 8 u} ^h _{o -} C _d C ⁴ ₂ ⁴ %A ^% A A ^{1 5 + +} A _d ^{0 4} ₀ ⁷ %N _{+ -} ^{1 1 n} ₄ D _C D ₂ ¹ _L ^{6 O} ₇ ³ _L ^{0 O} ₁ ¹ N ^{% T} ₀ ⁷ ₁ NN _{C C a C C + C + C + C + F} ^X _P ^D _{S β} ^D _{S β r} ^a _l ^{d u} _n % ⁰ % ^{0 %} l ^{%%% l} _x ^a _{e e} ^{i C} _r ^{s r} ₁ ⁶ ₇ ² % ^%% ₀ i _u ^t _{+ +} ^{% 0} ₃ % _{0 0} ^{5 %} 3 ₀ ⁵ ₀ % ⁶ _{0 -} ⁹ _{0 -} ⁸ % - % ^{%0 %} 5 ₀ ^{%%% 7} _{0 0 0} ⁷ a ^t _{a s} ^e _c r ^u _{1 t} M _h A ₁ A ₀ ^{7 %} ₀ ¹ ₊ ⁰ ₉ ⁸ ₂ ^{4 +} - ₃ ⁺ ₂ C ⁺ ₀ ⁶ ₁ A ₁ A ₁ ^% A ₀ ^{8 0} _{0 0} ⁷ - ² ₊ ^% ₀ - ^{4 4 1} - ⁴ - - 1 ₃ ^{C x t} _{r n} ^{t 1 5} - ⁹ - ₁ ⁺ D E ^y _{s LL s} ^{O N} _R N - ^{1 3 5} - ¹ - _{1 2 - L} AD _{R C} ^O C _C ^T D _P NXMOA ^A D ^B _F ^O _L ^U _L ^L _P ^P _{S C} N _LLL ^NT NNXXHOA V _β ^G B ^O C ^O C ^O C _C D _P D ^B _F ^B _F ^O _L ^O _L ⁴ _P ^L _P ^P _{S 1} O ^W ₃ ⁰ ₀ ⁰ - ¹ ₇ ⁷ ₁ ⁵ : _t ^e _k ^c _o ^{D y} _e ⁿ _r ^ot _t A g _n ⁱ _g ^a _-i ^t _n ^a e ^v i _t ⁿ _e ^v _e ^r _P - _a ^{r a} _{l x} ⁱ _r ⁱ _t g _{t n} ^{x u} _l ^{l i} _Ee ^t _a ^c _e ^{t 1} _P ^% ₀ ³ _P % ^{0 1} _P % ^{0 3} _P % ⁰ g C M _o ^{r a} _p M ⁰ ₀ M _{5 8 7} - _i M ¹ ₊ ^M2 M + _γ M ⁷ M + M ² _{+ γ} t _n ^a _{n e} ^{o % v} ₀ ^% i _n t ^o _{i i} ^s _e ⁸ % a ^{s 0} % ₀ ^{0 r} _e ^h u ^h _{o 1 + 5 9 1 1} ⁰ _{1 1} C A ^% ₀ A ⁺ A ^% ₀ A ^{1 +} C _d ⁴ A _d ⁿ _L ^{7 1 4 O} ₂ M A _{C L} ^{3 7 O} _{0 L} ^% ₊ ^{1 O} _{0 1 C a C} ¹ _{+ L} ^D _{S α C} ² _{+ C} ⁷ ₊ ^N _F ^D _{S α r} ^a _l ^{d u} _{n l} ^l _x ^a _e % ^% ₀ ^% e ^{i C} _{r a} ^{t s r} a ⁱ _{s u} ^{t % e} _{c 0} ^{5 %} ₀ % ^{0 % 0} ₆ ⁶ ₀ ^{% 7} ₀ % ^{0 %} ₀ ⁶ _{0 -} % ^{7 %} ₀ ^% _{0 2} ⁴ _{- 8} ^{+ 5} ₁ ^% ₀ ⁰ ₁ ^{1 5} - ^{3 r} _t M _h ^u _{r 4} ^{+ 6} _{- 0} ¹ - ₊ ⁺ _{3 2} ⁺ A ⁵ _{- 0} ¹ - ₊ ¹ ₁ ^{+ x t} _n ^{t y} _s N ^N ₂ DN C ^T NMO ^A N ³ _L ^NT _{2 L} NXM E _s ^G B D _P D ^B _F ^U _L ^L _{P C} V _β ^G B ^O C _C D _P D ^B _F ^O _L ^U _{L 1} O ^W ₃ ⁰ ₀ ⁰ - ¹ ₇ ⁷ ₁ ⁵ : _t ^e _k ^c _o ^{D y} _e ⁿ _r ^ot _t A g _n ⁱ _g ^a _-i ^t _n ^a e ^v i _t ⁿ _{, e} ^v _a ^{v h} _t ^d _a % _{0 0 0 0} w ^{0 0} ₁ ^{6 5 7} e ^r _{i P} ^v _r ^w _n ^e ₉ ^{+ +} _{+ + +} ^{% u} _{o S} ^r _g ^a _n ^e _r ² _L % ^{0 C} ₇ G ^R ₁ T ₂ T ₆ T _C0 ⁵ _{0 B} ¹ ₊ ^S _{S R B} ^N _I ^I _{R S} ^I _{R S} ^I _S ^N _T ¹ _{+ β} n _i ^z _i ^r _u ^t _s ⁱ _{g o} ¹ _P % ^{0 2} % Q ₈ M A ¹ _S ⁰ +A ₃ H ⁶ _{+ α 0} ¹ ₁ - _{a r} r ^a _{x n} ^{oi g} _{t l} x ^{u i} l ^l _{r e} ^t _{t a} ^c _e ^{t 1} _P ^% ₀ ³ _P % n ⁱ _{E g} C M _o ^r M ⁰ ₀ ^{0 a} _p ¹ M ₁ - _i M ₊ M ¹ _{+ γ} t _n ^a _{n e} ^{o v} _{i n i} ^{s %} ₀ t ^o _i % ^% _{0 a} ^s _e ^{h 8 r} _{e o +} ⁰ ₇ ⁴ _{1 u} ^h C ₂ ^{4 3} ₊ ⁺ C _d ¹ A _d ⁿ _{C1 C a} ^D _C ^N _F ^D _{S α r} ^a _l ^d _n % e ⁰ % ^{% u} _l ^l _x ^a e ⁱ _r ^{s r} ₃ ^{2 %0 i} _u ^t _{+ 0 2} ^% ₀ 1 ₀ ^{6 4} ₂ C _a ^t _{a s} ^e _c ^{3 r} _t M _h x ^{t u} _{1 r 5 + -} ⁺ n ^t A ^{3 +} _{1 3} ^C E ^y _{s L} MAD _{R s} ^O HOA C ^U _L ⁴ _P ^L _P ^P _S Attorney Docket: 51771-0003WO1 [00378] Table 22 shows the effect compared to replicated NHDF. [00379] Table 22. Compared to r _{eplicated NHDF} ^{replicated NHDF + 48h of treatment} % % % % % % % % % % Example 17: Effect of A2M and sKL on Skin Cell Inflammation Attorney Docket: 51771-0003WO1 [00380] This example assesses the effect of A2M (Sigma Aldrich, Cat. No. SRP6314-1, from human plasma) and sKL (Biotechne, aa 34-981, Cat. No.5334.KL.025) on gene expression in human skin cells. Tests were performed on Normal Human Dermal Fibroblasts (NHDF, 68 years old, woman). [00381] The conditions tested were: (i) NHDF; (ii) Replicated NHDF untreated; (iii) Replicated NHDF + sKL 0.05μM 48h; (iv) Replicated NHDF + A2M 0.5μM 48h; (v) Replicated NHDF + sKL /A2M 0.05μM/0.5μM 48h; (vi) Replicated NHDF + sKL 0.05μM 8 weeks; (vii) Replicated NHDF + A2M 0.5μM 8 weeks; and (viii) Replicated NHDF + sKL /A2M 0.05μM/0.5μM 8 weeks. [00382] Non-replicated NHDFs were grown on a single population doubling. Non- replicated NHDFs were seeded on at a concentration of 10,000 cells per well in 96-well plate in the presence of suitable culture media (Promocell). [00383] Replicated NHDF 48h were grown on 12 populations doubling (8 weeks). The culture was carried out in 12-well plate with appropriate medium. After the replication phase, cells were seeded at a concentration of 10,000 cells per well in 96-well plate in the presence of suitable culture media (Promocell). After adhesion (one day), the tested proteins at the chosen concentration were added for 48 hours. [00384] Replicated NHDF 8 weeks were grown on 12 populations doubling (8 weeks) and were exposed to the test proteins during all the phase of replication. The treatment with the protein was changed twice a week. These cells were growth in 12-well plate with appropriate medium. After this replication phase, cells were seeded at a concentration of 10,000 cells per well in 96-well plate in the presence of suitable culture media (Promocell). After adhesion (one day), the tested proteins at the chosen concentration were added for 48 hours. [00385] Quantification of inflammation markers was performed on the supernatant of cells collected after seeded in 96-well plate and 48h of treatment. [00386] At the end of the treatment, the supernatants were collected and put in contact with beads of different size and internal fluorescence intensity. Beads were conjugated with specific antibody targeting inflammation mediators. These beads were differentiated by their size and internal fluorescence intensity by flow cytometry (MACSQuant® Analyzer 10 Flow Attorney Docket: 51771-0003WO1 Cyrtometer – Miltenyi Biotec) allowing to separate specific cytokine populations and quantify them. The mean of the concentration of the different cytokines was quantified and expressed in pg/mL +/- Standard error of the mean (SEM) was presented. The values were related to the untreated control to express an activating or inhibiting effect. To compare the means, a Mann- Whitney test was used with GraphPad Prism Software® (ns>0.05, *<0.05, **<0.01, ***<0.001 and ****<0.0001). [00387] Successive NDHF replication for 8 weeks resulted in a significant change in the secretion of the cytokine MCP-1 and IL-6 compared to non-replicated NHDF (Table.22). Treatment of replicated cells for 48 hours with sKL resulted in significant modulation of 4 cytokines: MCP-1, IL-6, IL-10 and IL-23 (Table.23). Treatment of replicated cells for 48 hours with A2M led to a significant modification of all tested cytokines (i.e., IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33) (Table.23). The same is true for the combination of A2M and sKL (Table.22). [00388] For cells replicated for 8 weeks with A2M and/or sKL, sKL modulated 4 cytokines: IFN-α2, MCP-1, IL-6 and IL-23; A2M resulted in a change in all cytokines except IL- 1β; and the combination of sKL and A2M resulted in a variation of all tested cytokines (Table. 22). [00389] Table 23. R-NHDF = replicated NHDF; NA = not applicable; ns>0.05, *<0.05, **<0.01, ***<0.001 and ****<0.0001 Untreated 48 hours 8 weeks + ** Attorney Docket: 51771-0003WO1 Untreated 48 hours 8 weeks + Attorney Docket: 51771-0003WO1 Example 18: Effect of A2M and sKL on Proteins Expression in Skin Cells [00390] The test was carried out on Normal Human Dermal Fibroblasts (NHDF, 68 years old, woman) using A2M (Sigma Aldrich, Cat. No. SRP6314-1MG) and/or sKL (R&D Systems, Cat. No.5334-KL-025). The conditions tested were: (i) NHDF untreated; (ii) Replicated NHDF untreated; (iii) Replicated NHDF + sKL 0.05μM 48 hours; (iv) Replicated NHDF + A2M 0.5μM 48 hours; (v) Replicated NHDF + sKL /A2M 0.05μM/0.5μM 48 hours; (vi) Replicated NHDF + sKL 0.05μM 8 weeks; (vii) Replicated NHDF + A2M 0.5μM 8 weeks; and (viii) Replicated NHDF + sKL /A2M 0.05μM/0.5μM 8 weeks. ) [00391] Non-replicated NHDFs were grown on a single population doubling. NHDF non- replicated were seeded on at a concentration of 10,000 cells per well in 96-well plate in the presence of suitable culture media (Promocell). [00392] Replicated NHDF 48 hours were grown on 12 populations doubling (8 weeks). The culture was carried out in 12-well plate with appropriate medium. After the replication phase, cells were seeded at a concentration of 10,000 cells per well in 96-well plate in the presence of suitable culture media (Promocell). After adhesion (one day), the tested proteins at the chosen concentration were added for 48 hours. [00393] Replicated NHDF 8 weeks were grown on 12 populations doubling (8 weeks) and were exposed to the test proteins during the entire phase of replication. The treatment with the sKL and/or A2M was changed twice a week. The cells were growth in 12-well plate with appropriate medium. After this replication phase, cells were seeded at a concentration of 10,000 cells per well in 96-well plate in the presence of suitable culture media (Promocell). After adhesion (one day), the tested proteins at the chosen concentration were added for 48 hours. [00394] For immunofluorescence, after treatment, the cells were washed and fixed with Formalin. After permeabilization, the selected markers (P16Ink4a, p21, p53, lamin B1, γH2AX, collagen I, collagen III, and collagen IV) were specifically detected by Immunofluorescence. The labeled proteins were observed and quantified on 1000 cells by wells by automated fluorescence microscopy Cellinsight CX7 High-Content Screening Platform (Thermofisher). The average fluorescence intensity ± standard error to mean (sem) was represented. Attorney Docket: 51771-0003WO1 [00395] For beta-galactosidase staining, after treatment, the cells were washed and fixed with Formalin. The β-Galactosidase was specifically detected using a staining solution. The labeled proteins were observed and quantified by automated fluorescence microscopy Cellinsight CX7 High-Content Screening Platform (Thermofisher). The number of positive cells ± standard error to mean (sem) was represented. [00396] To compare the means, a Mann-Whitney test was used with GraphPad Prism Software® (ns>0.05, *<0.05, **<0.01, ***<0.001). [00397] The results are depicted in Table 24. [00398] Table 24. Summary of sKL/A2M treatment effect on replicated NHDF (R- NHDF); bold = positive effect; italics = negative effect; all others = similar, not significant 48 hours 8 weeks F * * * [00399] The expression of proteins implicated in cell cycle arrest (P16ink4a, P21, P53) increased with the cell replication (Table 24). Only A2M treatment during 48 hours allowed reduced P16 and P53 expression compared to untreated replicated NHDF (Table 24). After 8 weeks of sKL/A2M treatment, P21 level significantly decreased compared to untreated Attorney Docket: 51771-0003WO1 replicated NHDF (Table 24). sKL regulated the cellular lifespan of human cells by repressing p53 and negatively regulating p21 protein levels (Table 24). [00400] Concerning Lamin B1 and Beta-galactosidase activity, two senescence biomarkers, a positive effect of cell protection was quantified with the A2M treatment for 8 weeks (Table 24). The result with the sKL/A2M treatment for 8 weeks was mitigated because the Lamin B1 expression increased to protect the nucleus but the beta galactosidase activity increased like in senescent cells (Table 24). [00401] A very low γH2Ax staining in nuclei was found in all conditions. The replication doesn’t seem to cause DNA damages. [00402] An increase of Collagens expression was analyzed after replication cycle. Collagen I and IV expressions decreased to tend to the level of non-replicated cells, in particular with 8 weeks of treatment (Table 24). Collagen III expression increased in particular with 8 weeks of treatment (Table 24). [00403] In summary, a synergistic effect was observed for A2M and sKL. Collectively, A2M in combination with sKL inhibited p16, p21, and p53, and increased Lamin B1 for the 8- week treatment. These data follow the observation of inhibition of senescence. Additionally, the A2M and sKL combination treatment increased collagen III production significantly for the 8- week treatment group. Throughout replication, collagen types I and IV levels fell. For the 48- hour treatment, sKL, alone or in combination with A2M, inhibited p16, p21, p53, and beta-gal at 48 hours, which follows the observation of inhibition of senscence. In addition, for the 48-hour treatment, throughout early replication collagen types I, III and IV levels fell. There was little in the way of DNA damage in either the 48 hour or 8 week treatment protocols. [00404] To conclude, a beneficial effect akin to a senolytic drug or anti-aging property was found with A2M or sKL and A2M. This effect was enhanced with a long-term treatment. Example 19: Effect of A2M and sKL on SARS-CoV-2-infected cells [00405] Vero E6 cells were pre-treated with A2M (Sigma Aldrich, Cat. No. SRP6314- 1MG) or sKL (R&D Systems, Cat. No.5334-KL-025) for 24 hours and then infected with SARS-CoV-2 delta strain at an MOI of 0.001. One hour post-infection, supernatant was Attorney Docket: 51771-0003WO1 removed and the cells were treated again with A2M or sKL.24 hours after infection, supernatant was harvested for RT-qPCR to determine SARS-CoV-2 gene E copy number. Cells were untreated or treated with remdesivir as controls. Treatment with 2µM A2M and with 0.175µM sKL triggered a significant reduction in viral titer compared to the untreated condition, around 2 log10 and 1.3 log10, respectively. See Table 25. [00406] Table 25. Antiviral effect on Vero E6 cells infected with SARS-CoV-2 delta strain. * = p<0.05, **=p<0.005; ***p<0.001 (Student t test). Compound (µM) SARS-CoV-2 gene E Delta (log10) [00407] Calu-3 cells were pre-treated with A2M or sKL for 24 hours and then infected with SARS-CoV-2 delta strain at an MOI of 0.01. One hour post-infection, supernatant was removed and the cells were treated again with A2M or sKL (single dose experiment). For two the two-dose experiment, the cells were treated again with A2M or sKL at 18 hours after infection (two dose experiment). 48 hours after infection, supernatant was harvested for RT- qPCR to determine SARS-CoV-2 gene E copy number. Cells were untreated or treated with remdesivir as controls. The two dose A2M treatment at a dose of 2 µM significantly reduced SARS-CoV-2 gene E copy number (Table 26). Single and two dose treatment with 0.175 µM of Attorney Docket: 51771-0003WO1 sKL or with two doses of 0.1 µM sKL significantly reduced SARS-CoV-2 gene E copy number (Table 26). [00408] Table 26: Antiviral effect on Calu-3 cells infected with SARS-CoV-2 delta strain. *= p<0.05 ***- p<0.0005 ****= p<0.0001 Single Dose Two Dose Example 20: Effect of A2M and sKL on Vaccinia Virus-Infected Cells [00409] Vero E6 cells were plated and subsequently pre-treated with A2M (Sigma Aldrich, Cat. No. SRP6314-1MG) and/or sKL (R&D systems; 5334-KL-025) at various concentrations. A2M and sKL were determined to be non-toxic at 2 µM or less (A2M) and at 1 µM or less (sKL) (data not shown). 24-hours post-treatment, cells were infected with VacV- ANCHOR at MOI=0.015 for 48 hours. To evaluate antiviral activity, cells were fixed 48 hours- post infection, stained with PBS Hoechst 33342 (1mg/mL), and imaged to quantify the infection rate and replication rate. To evaluate proteasome activity, cells were lysed (50 mM Tris–HCl pH 7.4, 1% NP-40, 0.1% SDS, and 150 mM NaCl) 48 hours-post infection, treated with the Protease Attorney Docket: 51771-0003WO1 Inhibitor Cocktail (Thermofisher scientific) for 30 minutes in ice, and centrifuged at 14,000 rpm at 4°C for 20 minutes. The supernatant fraction was collected in a new tube and the proteasomal activity was measured using the 20S Proteasome Activity Assay kit according to the manufacturer’s instructions (Cat. No APT280 Chemicon Inc., CA, USA). [00410] At high concentrations, both compounds were cytotoxic or cytostatic on Vero-E6 cells; the toxicity was negligible at 1μM A2M and 0.25μM sKL. (FIG.58). The infection rate reached 54% in non-treated control Vero-E6 cells 48 hours post-infection in this experiment when using VacV ANCHOR at a MOI of 0.015 (FIG.59). Cells treated with A2M at 2μM were less infected compared to non-treated condition and sKL at 0.5μM had an antiviral effect (FIG. 60); however, A2M and sKL were toxic under these conditions. At non-toxic concentrations (A2M 1 μM and sKL 0.25 μM), the infection rates were lower than in the non-treated condition (FIG.60). Combination of A2M and sKL at 1μM A2M/0.1μM sKL resulted in the best antiviral results (FIG.60). At these concentrations no toxicity was observed, the infection rate was reduced by 30%, and the replication rate was reduced by 68% to 50%. See FIGs.59-61. [00411] In the proteasome activity assay, treatment with A2M and sKL prevented infection-dependent increase of proteasome activity. Combination of A2M/sKL reduced the 20S proteasome activity by 50%. See FIG.62. Example 21: Cytotoxicity of A2M and sKL on Skin Cells [00412] Cytoxicity studies were performed on normal human epidermal keratinocytes (NHEK, 63 years old, woman) and on Normal Human Dermal Fibroblasts (NHDF, 68 years old, woman). A2M was not toxic for NHEK cells nor for NHDF, even at 2.5 µM. sKL was not toxic for NHEK cells at 0.005 µM and for NHDF cells at 0.005 µM. Combined, the cytotoxicity limit for NHEK cells was 0.005 μM of sKL with 0.05 μM of A2M and 0.25 μM for sKL with 1.25 μM of A2M for NHDF cells. Example 22: Effect of A2M and sKL on Superoxide Dismutase (SOD) [00413] This example evaluates the effect of sKL (Bio-Techne, Catalog No.5334.KL.025; amino acids 34-981) and A2M (Sigma-Aldrich, Cat. No SRP6314-1) on superoxide dismutase (SOD) in skin tissue. Skin explants were prepared and treated with sKL and A2M as described Attorney Docket: 51771-0003WO1 in Example 15. Following the 7 day treatment, the skin explants were crushed, and the SOD enzyme activity was detected by spectrophotometry after the transformation of superoxide anions. The optical densities were converted in Units of activity by mL via a standard curve. SOD1, SOD2, and SOD3 were analyzed. [00414] The mean of the SOD Units/ml was calculated for each donor and for the combination of the two donors (“global”) and the values are compared to the untreated control (100%) to express an activating or inhibiting effect. A statistical Student test was carried out on data using GraphPad Prism Software® (ns>0.05, *<0.05, **<0.001 and ***<0.0001). See Table 27. SOD enzyme activity significantly increased with treatment with A2M and sKL. [00415] Table 27. SOD activity SOD Activity (%, compared Example 23: Treating Alzheimer's Disease in a Patient Using A2M and/or sKL [00416] A patient with Alzheimer's disease is treated by the methods described hereinabove. Briefly, a subject is diagnosed as having Alzheimer's disease based on the outcome of one or more cognitive tests, laboratory tests, and/or biomarker assays. For example, a subject is diagnosed as having Alzheimer's disease based on the outcome of one or more cognitive tests, such as, one or more of Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Clinical Dementia Rating Scale (CDR), Montreal Cognitive Assessment (MoCA), and/or neuropsychological tests. Additionally, or in the alternative, a subject is diagnosed as having Alzheimer's disease based on the outcome of one or more laboratory tests, such as, one or more blood tests for comprehensive metabolic panel (CMP), vitamin B12 and folate levels, inflammatory markers, and Apolipoprotein E (APOE) genotyping. Additionally, or in the alternative, a subject is diagnosed as having Alzheimer's Attorney Docket: 51771-0003WO1 disease based on the outcome of assay(s) for NfL and/or YKL-40. Additionally, or in the alternative, a subject showing one or more symptoms of Alzheimer's disease is diagnosed as having Alzheimer's disease. [00417] Such a patient with Alzheimer's disease (e.g., a subject diagnosed as having Alzheimer's disease and/or showing symptom(s) of Alzheimer's disease) is then treated by administering A2M and/or sKL according to the present methods. Briefly, a therapeutically effective amount of an A2M protein (e.g., comprising the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 4, and/or SEQ ID NO: 6) and/or a therapeutically effective amount of a sKL protein (e.g., comprising the amino acid sequence of SEQ ID NO: 15) is administered to the patient. For example, the therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered to the patient at a stoichiometric ratio of A2M:sKL of about 1:1, about 2.5:1, about 5:1, about 10:1, about 11:1, about 12:1, or about 50:1. The therapeutically effective amount of the A2M protein and the therapeutically effective amount of the sKL protein are administered as a single composition or as two separate compositions. [00418] To assess the effectiveness of the treatment, the patient is monitored periodically (e.g., during and/or after treatment) using one or more cognitive tests, laboratory tests, and/or biomarker assays. The dosage and/or duration of the treatment is determined based on the outcome of such tests. Following treatment, the patient shows one or more of: improved cognitive function(s); decrease in level of one or more inflammatory markers; increase in level of vitamin B12 and/or folate; decrease in level of NfL and/or YKL-40; and/or decrease in neurodegeneration. Example 24: Delivery of A2M and/or sKL by Exosomes [00419] This example describes the delivery of A2M and/or sKL proteins by exosomes. In particular, A2M protein (e.g., comprising the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 4, and/or SEQ ID NO: 6) and/or sKL protein (e.g., comprising the amino acid sequence of SEQ ID NO: 15) are artificially loaded into exosomes for targeted delivery to specific cells, such as, to target cells in a patient (e.g., a patient described in the foregoing example). Attorney Docket: 51771-0003WO1 [00420] Briefly, A2M protein and/or sKL protein described herein are artificially incorporated into exosomes by a chemical method. For example, A2M protein and/or sKL protein are mixed with exosomes, and then certain chemicals are added to the mixture to promote the uptake of the A2M and/or sKL proteins into the exosomes. [00421] Additionally, or in the alternative, A2M protein and/or sKL protein are artificially incorporated into exosomes by transfection. For example, exosomes are mixed with polynucleotides (e.g., DNA) encoding A2M and/or sKL (e.g., polynucleotide encoding A2M, polynucleotide encoding sKL, and/or polynucleotide encoding both A2M and sKL). Following delivery of such exosomes into cells (e.g., using liposomes or electroporation), the polynucleotides encode the A2M and/or sKL proteins, and the A2M and/or sKL proteins thus produced get packaged into the exosomes. [00422] Additionally, or in the alternative, A2M protein and/or sKL protein are artificially incorporated into exosomes by electroporation. For example, an electric field is used to introduce large amounts of the A2M and/or sKL protein into exosomes. [00423] Exosomes loaded with A2M and/or sKL proteins are then administered to patients instranasally (e.g., by inhalation), subcutaneously, and/or intravenously, resulting in delivery of high amounts of functional A2M and/or sKL proteins to specific target cells. Example 25: Toxicokinetic Studies of A2M and soluble Klotho (sKL) in Male/Female C57BL/6 Mouse Following Subcutaneous Administration [00424] This example evaluates the potential toxicities of A2M and sKL when administered to male/female C57BL/6 mice via subcutaneous injection (SC). Table 28 provides a description of the test groups and the sample collection schedule for each group. [00425] Table 28. M=male; F=female; h=hours N Sample Collection Times R ^{i o./Sex of} r 1 Attorney Docket: 51771-0003WO1 Daily (2W, Every 0.6 mg/kg [24h], Day 5 [24h], Day 9 3 other day) A2M+0.15mg/kg 12M&12F ^{[24h], Day 13 [24h]} KL ] , [00426] During the dosing period, clinical observations were observed daily and no clinical signs were observed in the nine groups. Body weights were measured and recorded twice a week during the whole study. The growth rate of average body weight of each group dosed with test article was no difference among that observed in vehicle group. [00427] For the single dose administration of A2M or sKL, serum A2M level was increased from 5 minutes to 24 hours timepoint with Cmax 4513 pg/mL at 2.5 mg/kg A2M dose and sKL level was increased up to 2961.7 pg/mL at 4 hours and dropped after 12 hours with 0.3 mg/kg sKL dose. Anti-human A2M and sKL antibody were not detectable in both pretreatment and endpoint of the experiment. [00428] For the multiple dose administration of A2M and sKL, serum A2M level was increased to the highest concentration (1192.2 ng/mL) on Day 5 (24 hours) then dropped after Day9 (24 hours) rapidly. Serum sKL level was increased from Day 1(24 hours), decreased after Day9 (24 hours) and remained stable on Day 13 (24 hours). Both of anti-human A2M and sKL antibody were detectable and increased from day 9 (24 hours) to day 13 (24 hours) which explains the decrease of A2M and sKL after Day 9 (24 hours). Example 26: Pharmacokinetic Studies of A2M and soluble Klotho (sKL) in Male/Female C57BL/6 Mouse Following Subcutaneous Administration [00429] This example evaluates the potential pharmacokinetics of A2M and sKL when administered to male/female C57BL/6 mice via subcutaneous injection (SC). Table 29 provides a description of the test groups and the sample collection schedule for each group. Attorney Docket: 51771-0003WO1 [00430] Table 29. M=male; F=female; h=hours Se s _{e level} ^No./Sex rum Collection Times G _{roup Do} ^of M _ice Relative to Dose [00431] For mice administered A2M and sKL, the average exposure AUClast in serum was significantly improved compared with mice dosed only with A2M or only with sKL. Tables 30- 33. [00432] Table 30: Mean (n=3) Pharmacokinetic Parameters of A2M after SC Dose of 0.6 mg/kg A2M+0.15 mg/kg sKL in Mice for Group 2. T1/2=half-life; MRT=mean residence time; Vz=volume of distribution; CL = clearance; F = bioavailability. Route SC C ^{om ound} _{A2M A2M A2M} e [00433 ose of 0.6 mg/kg A2M in Mice for Group 3 Route SC e Attorney Docket: 51771-0003WO1 Dose (mg/kg) 0.6 T _1/2 (hr) NA NA NA [00434 se of 0.6 mg/kg A2M+0.15 mg/kg sKL in Mice for Group 2 Route SC C ^ompound _{KL KL KL} e [00435 ose of 0.15 mg/kg sKL in Mice for Group 4 Route SC e Attorney Docket: 51771-0003WO1 T _max (hr) 1.00 1.00 1.00 C _max (pg/mL) 850 657 753 Example 27: Toxicokinetic Studies of A2M and soluble Klotho (sKL) in Male/Female New Zealand White Rabbit Following a Subcutaneous Administration [00436] This example evaluates the potential toxicokinetics of A2M and sKL when administered to male/female New Zealand White rabbits via SC injection. Table 34 provides a description of the test groups and the sample collection schedule for each group. [00437] Table 34. M=male; F=female; h=hours N ^{o./Sex of} Serum/blood Collection G _{roup Regimen Dose level} Times Relative to Dose 4 h h h, h m at [0 Table 34). For the A2M and sKL following SC administration in rabbit with multiple dose (Phase I study), serum A2M level was increased (5.2 ng/mL to 621.0 ng/mL) from 2h to 24h on day1 at the dose of 300 ug/kg A2M+10 ug/kg sKL (D1 to D3). Serum A2M level was decreased Attorney Docket: 51771-0003WO1 (1599.0 ng/mL to 1023.0 ng/mL) from 2h to 24h on day4 at 10 ug/kg sK dose (D4 to D6). Serum A2M level was around 0 ng/mL from 2h to 24h on day7 at 300 ug/kg A2M (D7 to D9), day10 at 500 ug/kg A2M+15 ug/kg sKL dose (D10 to D12) and day13 at 500 ug/kg A2M (D13 to D15). Serum sKL level was at similar level from 2h to 24h on day1 at 300 ug/kg A2M+10 ug/kg sKL dose (D1 to D3), day 4 at 10 ug/kg sK dose (D4 to D6), and day 7 at 300 ug/kg A2M (D7 to D9) dose. Serum sKL level was increased markedly increased and kept at high level (3225.0 pg/mL to 2695.0 pg/mL) from 2h to 24h on day 10 at 500 ug/kg A2M+15 ug/kg sKL dose (D10 to D12) and day 13 at 500 ug/kg A2M dose (D13 to D15). [00439] For the A2M and sKL following SC administration in rabbit daily at the dose for 2 weeks (Phase II study), serum A2M level was increased from 2h to 24h on day1 at 200ug/kg A2M+6ug/kg SkL and 100ug/kg A2M+3ug/kg sKL dose. A2M was at a low level from 2h to 24h on day14. Serum sKL level was increased to the highest concentration (737.8 ng/mL) at 12h and dropped at 24h on day1 at 200ug/kg A2M+6ug/kg SkL. Serum sKL was at low level from 2h to 24h on day1 at 100ug/kg A2M+3ug/kg sKL. sKL was at a much higher level (2226~3560 pg/mL concentration) and remained stable from 2h to 24h on day14 at 200ug/kg A2M+6ug/kg sKL. Serum sKL remained low level from 2h to 24h on day14 at 100ug/kg A2M+3ug/kg sKL. [00440] For the A2M and sKL following SC administration in rabbit daily at the dose for 2 weeks (Phase II study), rabbit anti-human A2M and sKL antibodies were not detected at pretreatment but detected at endpoint. The high level of anti-A2M antibody explained low concentration of A2M at endpoint (day14, 24h). Anti-sKL antibody didn’t affect serum sKL level on day 14. [00441] Results are also provided in Tables 35-51. [00442] Table 35: Mean (n=2) Pharmacokinetic Parameters of A2M after SC Dose of 300 ug/kg A2M+10 ug/kg sKL in Rabbits for Phase I Group1 (day 1-3) Route SC e Attorney Docket: 51771-0003WO1 A _{UC0-∞(hr*ng/mL)} ^{NA NA NA} A _{UC Extr(%)} ^{NA NA NA} [00443 Dose of 10 ug/kg s KL in Rabbits for Phase I Group1 (day 4-6) Route SC C ^ompound _{A2M A2M A2M} e [00444 ose of 300 ug/kg A2M in Rabbits for Phase I Group1 (day 7-9) Route SC e Attorney Docket: 51771-0003WO1 M _{RT0-∞ (hr)} ^{5.39 4.10 4.75} A _{UC0-∞ /D (hr*kg*ng/mL/mg)} ^{1569 64.6 817} [00445 ose of 500 ug/kg A 2M in Rabbits for Phase I Group1 (day 13-15) Route SC C ^ompound _{A2M A2M A2M} e [00446 ose of 200 ug/kg A2M+ 6 ug/kg sKL in Rabbits for Phase II Group3 Day 1 Route SC e Attorney Docket: 51771-0003WO1 V _{z (L/kg)} ^{NA NA NA} C _{L (mL/min/kg)} ^{NA NA NA} [00447 ose of 200 ug/kg A + 6 ug/g s n abbts or ase Group3 ay Route SC C ^ompound _{A2M A2M A2M} e [00448 ose of 100 ug/kg A2M + 3 ug/kg sKL in Rabbits for Phase II Group4 Day 1 Route SC e Attorney Docket: 51771-0003WO1 C _{L (mL/min/kg)} ^{NA NA NA} F _(%) ^{NA NA NA} [00449 ose of 100 ug/kg A + ug g s n a ts or ase roup ay Route SC C ^ompound _{A2M A2M A2M} e [00450 ose of 300 ug/kg A2M+10 ug/kg sKL in Rabbits for Phase I Group1 (day 1-3) Route SC e Attorney Docket: 51771-0003WO1 F _(%) ^{NA NA NA} [00451] Table 44: Mean (n=2) Pharmacokinetic Parameters of sKL after SC Dose of 10 ug/kg s n a s or ase roup (ay -) Route SC C ^ompound _{sKL sKL sKL} e [00452 ose of 300 ug/kg A2M in Rabbits for Phase I Group1 (day 7-9) Route SC e Attorney Docket: 51771-0003WO1 [00453] Table 46: Mean (n=2) Pharmacokinetic Parameters of sKL after SC Dose of 500 ug/kg A2M+15 ug/kg sKL in Rabbits for Phase I Group1 (day 10-12) Route SC C ^ompound _{sKL sKL sKL} e [00454 ose of 500 ug/kg A2M in Rabbits for Phase I Group1 (day 13-15) Route SC e [00455 ose of 200 ug/kg A2M+ 6 ug/kg sKL in Rabbits for Phase II Group3 Day1 Attorney Docket: 51771-0003WO1 Route SC C ^ompound _{sKL sKL sKL} e [00456 ose of 200 ug/kg A2M+ 6 ug/kg sKL in Rabbits for Phase II Group3 Day14 Route SC C ^d e [00457 ose of 100 ug/kg A2M + 3 ug/kg sKL in Rabbits for Phase II Group4 Day1 Route SC Attorney Docket: 51771-0003WO1 C ^ompound _{sKL sKL sKL} Gender Male Female Male & Female [00458 ose of 100 ug/kg A2M + 3 ug/kg sKL in Rabbits for Phase II Group4 Day14 Route SC C ^{m nd} e Attorney Docket: 51771-0003WO1 OTHER INSTANCES [00459] While the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.