CROSS-REFERENCES TO RELATED APPLICATIONS

[0001] This application claims priority and the benefit of U.S. Provisional Patent Application No. 63/119,573, filed November 30, 2020, the entirety of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

[0002] 1. FIELD OF THE INVENTION [0003] The present disclosure relates to therapeutic agents useful for the treatment of

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in humans. [0004] 2. DESCRIPTION OF RELATED ART

[0005] SARS-CoV-2 is an enveloped, positive-sense, single-stranded RNA coronavirus of the betacoronaviridae family and the pathogen is responsible for the global pandemic that causes the coronavirus induced disease in 2019 (COVID-19). Compared to the SARS-CoV and MERS-CoV outbreaks in 2002 and 2012, respectively, SARS-CoV-2 shows a lower fatality rate, but a much higher transmission rate, causing a greater threat to the public health and extraordinary social and economic burdens.

[0006] Infection of SARS-CoV-2 starts with the interaction of the trimeric viral spike (S) protein with human angiotensin-converting enzyme 2 (ACE2) receptor on airway epithelial cells, followed by viral entry and priming of human transmembrane protease serine 2 (TMPRSS2) that cleaves the S protein and initiates viral fusion. After entry, the viral genomic RNA is translated to polyprotein la (PPla) and polyprotein lab (PPlab), which are subsequently cleaved by a papain-like (PL) protease and a 3C-like (3CL) protease to form 16 non-structural proteins (Nspl-16) as a replication-transcription complex (RTC). Four structural proteins (spike, envelope, membrane, nucleocapsid) are encoded at the 3’ end and play important roles in virus maturation and infection. Replication of viral RNA from the N- to C-termini of PPlab is accomplished by RTC proteins such as RNA-dependent RNA polymerase (Rdrp, Nspl2). The viral proteins further undergo post-translational modifications (such as glycosylation) at the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), after which they are transported to the cell membrane for exocytosis. [0007] To date, the clinical management of COVID-19 is mostly based on supportive care, although several agents targeting viral replication and inflammation have been reported. Remdesivir, a Rdrp prodrug inhibitor, is the only antiviral agent to have received an emergency use authorization by the FDA for the treatment of COVID- 19. F avipiravir, an inhibitor of influenza Rdrp, was approved for the treatment of COVID-19 in Russia, China and India, but patients receiving the drug must be closely monitored to prevent adverse events; recently, the result of a phase 3 trial in Japan showed some positive effect. Hydroxychloroquine, especially in combination with a zinc supplement, has been reported to exhibit antiviral activity against RNA viruses, but the clinical use of hydroxychloroquine alone for the treatment of COVID-19 was halted due to a lack of significant benefit.

[0008] It is well known that RNA viruses have higher mutation rates than DNA viruses. Recently, a protein interaction map revealed 332 human proteins interacting with 27 SARS-CoV-2 proteins; a phosphoproteomic approach was further employed to expand the study of viral-host interaction. However, the proteomic analysis reported recently was only focused on the S protein and the detailed functions of glycosylation remained unclear. Nevertheless, the S protein is a promising target for development of neutralizing antibodies and vaccines due to its expression on the viral surface and its involvement in host cell entry. The S protein is highly glycosylated and broadly mutated, with approximately 85% of the sequence being changed, indicating the challenge in the development of effective vaccines or antibodies with broadly protective activity and the need to develop alternative therapies. However, development of new therapeutics often takes years; therefore, repurposing or repositioning of existing pharmaceuticals and herbal medicines for the treatment of COVID-19 has been considered as an attractive approach.

[0009] In the present disclosure, a library of 2,855 drugs approved for the treatment of human and animal diseases, as well as supplements and traditional Chinese herbal medicines were screened to identify the inhibitors of SARS-CoV-2 infection to Vero E6 cells. The effective compounds identified from the screening were further studied to establish the dose-response relationship and their in vivo anti-SARS-CoV-2 effects in hamsters infected with SARS-CoV-2. Accordingly, these compounds and/or extracts are potential candidates for the development of a medicament for treating SARS-CoV-2 infection. SUMMARY

[0010] The present disclosure is based on the unexpected discoveries that some known compounds and herbal extracts are effective in suppressing the activity of SARS-CoV-2 both in vitro and in vivo, as such, these compounds and/or herbal extracts as described herein are potential candidates for the development of a medicament for treating SARS- CoV-2 infection.

[0011] Accordingly, it is the first aspect of the present disclosure to provide a method for treating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in a subject. The method includes the step of administering to the subject an effective amount of an agent selected from the group consisting of an anti-viral agent, an anti- neoplastic agent, an anti-parasitic agent, an ion channel modulator, an antibiotic, an herbal extract, Soho tea, Reishi polysaccharide fraction 3 (RF3) of Ganoderma lucidum, and a combination thereof, so as to alleviate or reduce symptoms associated with the S ARS- CoV-2 infection.

[0012] Examples of the anti-viral agent suitable for use in the present method include, but are not limited to, nelfinavir (N-Bn), nelfinavir mesylate, and boceprevir.

[0013] Example of the anti-neoplastic agent suitable for use in the present method includes, but is not limited to, cepharanthine. [0014] Examples of the anti-parasitic agent suitable for use in the present method include, but are not limited to, emetine, ivermectin, moxidectin and mefloquine.

[0015] Examples of the ion channel modulator suitable for use in the present method include, but are not limited to, azelnidipine, dronedarone, ivacaftor and penfluridol [0016] Examples of the antibiotic suitable for use in the present method include, but are not limited to, monensin, and maduramicin.

[0017] According to preferred embodiments of the present disclosure, the agent is a combination of nelfinavir and ivermetin in a molar ratio of 1:1, a combination of cepharanthine and nelfinavir in a molar ratio of 2:1, or a combination of cepharanthine and ivermetin in a molar ratio of 2: 1. [0018] According to preferred embodiments of the present disclosure, the herbal extract suitable for use in the present method is a water extract of a plant selected from a group of families consisting of Lamiaceae, Mentheae, Asteraceae, Theaceae, Fabaceae,

Compositae, Saururaceae, Sapindaceae and Caprifoliaceae families. [0019] Examples of the plant of Lamiaceae family includes but are not limited to, Metha arvensis, Mentha haplocalyx, Nepeta tenuifolia, Ocimum basilicum, Perilla folium, Perilla frutescens, Prunellae Spica, Prunella vulgaris, Salvia hispanica, and Salvia rosmarinus. [0020] Example of the plant of Mentheae family includes, but is not limited to, Mentha haplocalyx or Metha arvensis.

[0021] Examples of the plant of Asteraceae family include, but are not limited to, Taraxacum mongolicum, Tussilago farfara, and Chrysanthemum morifolium.

[0022] Example of the plant of Theaceae family includes, but is not limited to, Camellia sinensis.

[0023] Examples of the plant of Fabaceae family include, but are not limited to, Arachis hypogaea, Glycyrrhiza uralensis, Glycyrrhiza glabra L, Glycyrrhiza inflate Batalin, and Spatholobus suberectus.

[0024] Examples of the plant of Saururaceae family includes, but are not limited to, Houttuynia cordata and Herba Houttuyniae.

[0025] Examples of the plant of Compositae family include, but are not limited to, Artemisia annua L., and Artemisia scoparia Waldst.

[0026] Examples of the plant of Sapindaceae family include, but are not limited to, Dimocarpus longan and Litchi chinensis. [0027] Example of the plant of Caprifoliaceae family includes, but is not limited to,

Lonicera japonica.

[0028] According to embodiments of the present disclosure, the herbal extract includes at least one compound selected from the group consisting of a flavonoid, flavan-3-ol, a caffeic acid derivative, a monoterpene, a diterpene, and a triterpene. [0029] According to some embodiments of the present disclosure, the Soho tea is a water extract of a combination of Perilla folium, Mentha haplocalyx, Prunellae spica, Houttuynia cordata, Artemisia annua L. , and Glycyrrhiza uralensis, in which the Perilla folium, the Mentha haplocalyx, the Prunellae spica, the Houttuynia cordata, the Artemisia annua L., and the Glycyrrhiza uralensis are respectively present in the amount of 40-75%, 10-30%, 0.1-2%, 1-4%, 5-15% and 5-15% by weight or volume in the combination.

[0030] According to other embodiments of the present disclosure, the Soho tea is a water extract of a combination of Perilla folium, Mentha haplocalyx, Prunellae spica, Houttuynia cordata, Lonicera japonica, Tussilago farfara, and Glycyrrhiza uralensis, in which the Perilla folium, Mentha haplocalyx, Prunellae spica, Houttuynia cordata, Lonicera japonica, Tussilago farfara, and Glycyrrhiza uralensis are respectively present in the amount of 40-75%, 10-30%, 0.1-2%, 1-4%, 1-10%, 1-10% and 5-15% by weight or volume in the combination.

[0031] According to embodiments of the present disclosure, the agent selected from the group consisting of an anti-viral agent, an anti-neoplastic agent, an anti-parasitic agent, an ion channel modulator, an antibiotic, and a combination thereof is administered in the amount of 0.01 to 500 mg/Kg to the subject.

[0032] According to alternative embodiments of the present disclosure, the agent selected from the group consisting of selected from the group consisting of an herbal extract, Soho tea, Reishi polysaccharide fraction 3 (RF3) of Ganoderma lucidum, and a combination thereof is administered in the amount of 0.01 to 5 g/Kg to the subject. [0033] Examples of the subject suitable for receiving treatment of the present disclosure include, but are not limited to, mammals. Preferably, the subject is a human.

[0034] Also within the scope of the present disclosure is the use of any of the agents described herein for the manufacture of a medicament for the treatment of SARS-CoV-2 infection described herein.

[0035] Many of the attendant features and advantages of the present disclosure will becomes better understood with reference to the following detailed description considered in connection with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The present description will be better understood from the following detailed description read in light of the accompanying drawings, where:

[0037] FIG 1 Evaluations of cell protective effect of Chinese herbal medicines in serial dilutions. Anti-SARS-CoV-2 infection effects of selected Chinese herbal medicines as water extracts (1.0 g/20 mL H ₂ O) and RF3 dissolved in H ₂ O (0.25 mg/mL) were presented as Log2(dilution fold); and

[0038] FIG 2 In vivo anti-SARS-CoV-2 assay conducted in female golden Syrian hamsters. (A) Body weight change after 3-day treatment, n=5 for test group and n=6 for the control group. (B) Virus elimination effect of drugs and extracts. Hamsters were infected with SAR-CoV-2 by intranasal instillation at day 0, and treated with drugs and extracts orally twice a day (30 mg/Kg/d for drugs and 200 mg/Kg/d for extracts) continuously for 3 days. After 3 days, the lungs were collected to measure the virus load (n = 5), *P<0.05; **P<0.005.

[0039] FIG 3 Evaluation of anti-SARS-CoV-2 effect of Soho Tea (formulation #1) in mice. (A) Body weight change after 6-day treatment. (B) Virus elimination effect of

Soho Tea in 3-day treatment. (C) Protection from virus infection with 12 h contact of

Soho Tea.

[0040] In accordance with common practice, the various described features/elements are not drawn to scale but instead are drawn to best illustrate specific features/elements relevant to the present invention. Also, like reference numerals and designations in the various drawings are used to indicate like elements/parts.

DESCRIPTION

[0041] The detailed description provided below in connection with the appended drawings is intended as a description of the present examples and is not intended to represent the only forms in which the present example may be constructed or utilized. The description sets forth the functions of the example and the sequence of steps for constructing and operating the example. However, the same or equivalent functions and sequences may be accomplished by different examples. [0042] 1. Definitions

[0043] For convenience, certain terms employed in the specification, examples and appended claims are collected here. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of the ordinary skill in the art to which this invention belongs. [0044] The term "administered", "administering" or "administration" are used interchangeably herein to refer a mode of delivery, including, without limitation, intraveneously, intramuscularly, intraperitoneally, intraarterially, intracranially, or subcutaneously administering an agent (e.g., a compound or a composition) of the present invention. In some embodiments, the compound of the present disclosure or a salt, a solvate thereof is formulated into tablets for oral administration. In other embodiments, t the compound of the present disclosure or a salt, a solvate thereof is formulated into powders for mixed with suitable carrier (e.g., buffer solution) before use, such as intraveneous injection. [0045] The term "an effective amount" as used herein refers to an amount effective, at dosages, and for periods of time necessary, to achieve the desired result with respect to the treatment of a disease. For example, in the treatment of SARS-CoV-2 infection, an agent (i.e., the present compound or herbal extract) which decrease, prevents, delays or suppresses or arrests any symptoms of the SARS-CoV-2 infection would be effective. An effective amount of an agent is not required to cure a disease or condition but will provide a treatment for a disease or condition such that the onset of the disease or condition is delayed, hindered or prevented, or the disease or condition symptoms are ameliorated. The effective amount may be divided into one, two or more doses in a suitable form to be administered at one, two or more times throughout a designated time period.

[0046] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in the respective testing measurements. Also, as used herein, the term "about" generally means within 10%, 5%, 1%, or 0.5% of a given value or range. Alternatively, the term "about" means within an acceptable standard error of the mean when considered by one of ordinary skill in the art. Other than in the operating/working examples, or unless otherwise expressly specified, all of the numerical ranges, amounts, values and percentages such as those for quantities of materials, durations of times, temperatures, operating conditions, ratios of amounts, and the likes thereof disclosed herein should be understood as modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the present disclosure and attached claims are approximations that can vary as desired. At the very least, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0047] The singular forms "a", "and", and "the" are used herein to include plural referents unless the context clearly dictates otherwise.

[0048] 2. Method of treatment

[0049] The present disclosure is related to therapeutic agents suitable for treating SARS- CoV-2 infection in a subject. Accordingly, the main objective of the present disclosure is to provide a method for treating a subject having SARS-CoV-2 infection. The method includes the step of administering to the subject an effective amount of an agent selected from the group consisting of an anti-viral agent, an anti-neoplastic agent, an anti-parasitic agent, an ion channel modulator, an antibiotic, an herbal extract, Soho tea, Reishi polysaccharide fraction 3 (RF3) of Ganoderma lucidum and a combination thereof, so as to alleviate or ameliorate symptoms associated with the SARS-CoV-2 infection.

[0050] Examples of the anti-viral agent suitable for use in the present method include, but are not limited to, nelfinavir (N-Bn), nelfinavir mesylate, and boceprevir.

[0051] Example of the anti-neoplastic agent suitable for use in the present method includes, but is not limited to, cepharanthine. [0052] Examples of the anti-parasitic agent suitable for use in the present method include, but are not limited to, emetine, ivermectin, moxidectin and mefloquine.

[0053] Examples of the ion channel modulator suitable for use in the present method include, but are not limited to, azelnidipine, dronedarone, ivacaftor and penfluridol [0054] Examples of the antibiotic suitable for use in the present method include, but are not limited to, monensin, and maduramicin.

[0055] According to preferred embodiments of the present disclosure, the agent is a combination of nelfinavir and ivermetin in a molar ratio of 1:1, a combination of cepharanthine and nelfinavir in a molar ratio of 2:1, or a combination of cepharanthine and ivermetin in a molar ratio of 2: 1. [0056] According to preferred embodiments of the present disclosure, the herbal extract suitable for use in the present method is a water extract of a plant selected from a group of families consisting of Lamiaceae, Mentheae, Asteraceae, Theaceae, Fabaceae, Compositae, Saururaceae, Sapindaceae and Caprifoliaceae families.

[0057] Examples of the plant of Lamiaceae family includes but are not limited to, Metha arvensis, Mentha haplocalyx, Nepeta tenuifolia, Ocimum basilicum, Perilla folium. _^ Perilla frutescens, Prunellae Spica, Prunella vulgaris, Salvia hispanica, and Salvia rosmarinus.

[0058] Example of the plant of Mentheae family includes, but is not limited to, Mentha haplocalyx or Metha arvensis. [0059] Examples of the plant of Asteraceae family include, but are not limited to,

Taraxacum mongolicum, Tussilago farfara, and Chrysanthemum morifolium.

[0060] Example of the plant of Theaceae family includes, but is not limited to, Camellia sinensis. [0061] Examples of the plant of Fabaceae family include, but are not limited to, Arachis hypogaea, Glycyrrhiza uralensis, Glycyrrhiza glabra L., Glycyrrhiza inflate Batalin, and Spatholobus suberectus.

[0062] Examples of the plant of Saururaceae family includes, but are not limited to, Houttuynia cordata and Herba Houttuyniae.

[0063] Examples of the plant of Compositae family include, but are not limited to, Artemisia annua L., and Artemisia scoparia Waldst.

[0064] Examples of the plant of Sapindaceae family include, but are not limited to, Dimocarpus longan and Litchi chinensis. [0065] Example of the plant of Caprifoliaceae family includes, but is not limited to,

Lonicera japonica.

[0066] According to embodiments of the present disclosure, the herbal extract includes at least one compound selected from the group consisting of a flavonoid (e.g., myricetin), flavan-3-ol (e.g., catechin or epigallocatechin gallate), a caffeic acid derivative (e.g., caftaric acid, rosmarinic acid methyl ester, or chlorogenic acid), a monoterpene (e.g., 1,

8-cineole or camphor), a diterpene (e.g., camosic acid or patchouli alcohol), and a triterpene (e.g., ursolic acid).

[0067] According to some embodiments of the present disclosure, the agent selected from the group consisting of the anti-viral agent, the anti-neoplastic agent, the anti- parasitic agent, the ion channel modulator, the antibiotic, and a combination thereof is administered to the subject in the amount of is administered to the subject in the amount of 0.01 to 500 mg/Kg to the subject, such as 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08,

0.09, 0.10, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10,

11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,

59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,

83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 110, 120, 130, 140,

150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 300, 310, 320, 330,

340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, or 500 mg/Kg. Preferably, the agent is administered to the subject in the amount of 10 to 300 mg/Kg, such as 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,

29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,

53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99,

100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270,

280, and 300 mg/Kg. More preferably, the agent is administered to the subject in the amount of 20 to 250 mg/Kg, such as 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,

34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,

82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, and 250 mg/Kg.

[0068] According to other embodiments of the present disclosure, the agent selected from the group consisting of the herbal extract, the Soho tea, the Rcishi polysaccharide fraction 3 (RF3) of Ganoderma lucidum is administered to the subject in the amount of 0.01 to 5 mg/Kg to the subject, such as 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0,

2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0,

4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5.0 g/Kg. Preferably, the agent is administered to the subject in the amount of 0.05 to 3.5 mg/Kg, such as 0.05, 0.06, 0.07, 0.08, 0.09, 0.10, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0,

2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5 g/Kg. More preferably, the agent is administered to the subject in the amount of 1.0 to 3.0 mg/Kg, such as 1.0,

1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0 g/Kg.

[0069] In certain embodiments, a drink or "Soho tea" prepared by extracting a combination of herbs and rhizome with hot water in a ratio of 1: 1 to 1:1,000 by weight or by volume is administered to a subject to protect the subject from being infected by the SARS-CoV-2 virus, or to reduce the viral load therein after the subject is exposed to SARS-CoV-2 virus.

[0070] In certain embodiments, one part (either weight or volume) of the combination of Per ilia Folium (or Perilla), Mentha haplocalyx (or Wild Mint Herb), Prunellae Spica

(or Prunella Spike), Houttuynia cordata (or Heartleaf Houttuynia), Artemisia annua L (or

Capillary Wormwood Herb), and Glycyrrhiza uralensis (or liquorice root and rhizome) is mixed with 1 to 1,000 parts (weight or volume) of hot water for sufficient time, such as 20 min, then remove the combination of herbs and rhizome (e.g., by filtering) to produce the drink, which is in the form of a solution. Preferably, the Perilla folium, the Mentha haplocalyx, the Prunellae spica, the Houtuynia cordata, the Artemisia annua L., and the Glycyrrhiza uralensis are respectively present in the amount of 40-75%, 10-30%, 0.1-2%, 1-4%, 5-15% and 5-15% by weight or volume in the combination.

[0071] In other embodiments, one part (either weight or volume) of the combination of Perilla Folium (or Perilla), Mentha haplocalyx (or Wild Mint Herb), Prunellae Spica (or Prunella Spike), Houttuynia cordata (or Heartleaf Houttuynia), Lonicera japonica (or Lonicerae Japonicae Flos), Tussilago farfara (or Quandong), and Glycyrrhiza uralensis (or liquorice root and rhizome) is mixed with 1 to 1,000 parts (weight or volume) of hot water for sufficient time, such as 20 min, then remove the combination of herbs and rhizome (e.g., by filtering) to produce the drink, which is in the form of a solution. Preferably, the Perilla folium, Mentha haplocalyx, Prunellae spica, Houtuynia cordata, Lonicera japonica, Tussilago farfara, and Glycyrrhiza uralensis are respectively present in the amount of 40-75%, 10-30%, 0.1-2%, 1-4%, 1-10%, 1-10%, and 5-15% by weight or volume in the combination.

[0072] According to embodiments of the present disclosure, the Soho tea is given to the subject as a drink, which can be consumed without limitation for at least 12 days, thereby rendering a protective effect (i.e., anti-SARS-CoV-2) to the subject, in which the viral load in the subject after being exposed to SARS-CoV-2 virus is lower than that of a control subject (i.e., the subject that receive water instead of Soho tea for 12 days). [0073] 3. Formulations

[0074] A further aspect of the present disclosure is to provide formulations for use in the present method. In some embodiments, one or more of the afore-described agents is/are formulated into dosage forms for administering to the subject.

[0075] The present formulation comprises one or more of the agents described above; and a pharmaceutically acceptable excipient. In some embodiments, the agent (e.g., mefloquine, nelfinavir, Nel/Iver (1:1), Cepha/Iver (2:1), Cepha/Nel (2:1), or extracts of Ganoderma luciudum, Perilla frutescens and Mentha haplocalyx) is mixed with pharmaceutically acceptable excipients to form a formulation for administering to the subject. In other embodiments, the agent (e.g., mefloquine, nelfinavir, Nel/Iver (1:1), Cepha/Iver (2:1), Cepha/Nel (2:1) or extracts of Ganoderma luciudum, Perilla frutescens and Mentha haplocalyx) is mixed with pharmaceutically acceptable excipients to form a formulation for administering to the subject. [0076] The agent (e.g., mefloquine, nelfmavir, Nel/Iver (1:1), Cepha/Iver (2:1), Cepha/Nel (2:1), extracts of Ganoderma luciudum, Perilla frutescens, and Mentha haplocalyx, or extracts of Ganoderma luciudum, Perilla frutescens, and Metha arvensis) may be present at a level of about 0.1% to 99% by weight, based on the total weight of the formulation. In some embodiments, the agent is present at a level of at least 1% by weight, based on the total weight of the formulation. In certain embodiments, the agent is present at a level of at least 5% by weight, based on the total weight of the formulation. In still other embodiments, the agent is present at a level of at least 10% by weight, based on the total weight of the formulation. In still yet other embodiments, the agent is present at a level of at least 25% by weight, based on the total weight of the formulation.

[0077] The formulation is prepared in accordance with acceptable pharmaceutical procedures, such as described in Remington’s Pharmaceutical Sciences, 17 ^th edition, ed. Alfonoso R. Gennaro, Mack Publishing Company, Easton, Pa ( 1985) . Pharmaceutically acceptable excipients are those that are compatible with other ingredients in the formulation and biologically acceptable.

[0078] The formulation is manufactured in accordance with the intended routes for its administration. For example, if the formulation is intended to be administered by oral ingestion, an enteric coating may be applied on the formulation so as to prevent the agent of the present invention from being degraded in the acidic environment or until it reaches the intestines of the subject. The formulation may further include additional components that help deliver the agent of the present invention to its intended target site. In some examples, the agents constituted the sensitizer is enclosed in a liposome to prevent it from enzymatic degradation, and to help transporting the agents through the circulation system of the subject, and/or across cell membrane to its intended cellular target site.

[0079] Further, the least soluble agent of the sensitizer may be formulated with additional agents, such as a solvating agent, an emulsifying agent and/or a surfactant, into a liquid formulation. Examples of the additional agent include, but are not limited to, cyclodextrin (e.g., a-cyclodextrin and b-cyclodextrin), and non-aqueous solvents, which include but are not limited to, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyl glycol, 1,3 -butyl glycol, dimethyl formamide, dimethyl sulfoxide, biocompatible oils (e.g., cottonseed oil, peanut oil, com oil, wheat germ oil, castor oil, olive oil, sesame oil, glycerol, tetrahydrogen furan, polyethylene glycol (PEG), fatty acid esters of sorbitan, and a combination thereof). [0080] The amount of the agent or herbal extract in the formulation varies with the route of administration. For example, formulations for acute treatment will contain larger amounts of the sensitizer, as compared to formulations that are for chronic treatment. Similarly, parental formulations will comprise less amounts of the present sensitizer, as compared to formulations that are for oral ingestion. Also within the scope of the present disclosure are formulations suitable for other administration routes.

[0081] Formulations may be in the form of liquids, solutions, suspensions, emulsions, elixirs, syrups, tablets, lozenges, granules, powders, capsules, cachets, pills, ampoules, suppositories, pessaries, ointments, gels, pastes, creams, sprays, mists, foams, lotions, oils, boluses, electuaries, or aerosols. [0082] 3.1 Formulation for Oral Ingestion

[0083] The agent of the present disclosure may be formulation into compositions suitable for oral ingestion. Formulations suitable for oral administration (e.g. by ingestion) may be presented as discrete units such as capsules, cachets or tablets, each containing a predetermined amount of the active compound; as a powder or granules; as a solution or suspension in an aqueous or non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion; as a bolus; as an electuary; or as a paste. [0084] A tablet may be made by conventional means, e.g., compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active compound in a free-flowing form such as a powder or granules, optionally mixed with one or more binders (e.g. povidone, gelatin, acacia, sorbitol, tragacanth, hydroxypropylmethyl cellulose); fillers or diluents (e.g. lactose, microcrystalline cellulose, calcium hydrogen phosphate); lubricants (e.g. magnesium stearate, talc, silica); disintegrants (e.g. sodium starch glycolate, cross-linked povidone, cross-linked sodium carboxymethyl cellulose); surface-active or dispersing or wetting agents (e.g. sodium lauryl sulfate); and preservatives (e.g. methyl p- hydroxybenzoate, propyl p-hydroxybenzoate, sorbic acid). Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. The tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active compound therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile. Tablets may optionally be provided with an enteric coating, to provide release in parts of the gut other than the stomach.

[0085] 3.2 Formulation for Parental Administration

[0086] Formulations suitable for parenteral administration (e,g. by injection, including cutaneous, subcutaneous, intramuscular, intravenous and mtradermal), include aqueous and nonaqueous isotonic, pyrogen-free, sterile injection solutions which may contain antioxidants, buffers, preservatives, stabilizers, bacteriostats, and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non- aqueous sterile suspensions which may include suspending agents and thickening agents, and liposomes or other mieroparticulate systems which are designed to target the agent to blood components or one or more organs. Examples of suitable isotonic vehicles for use in such formulations include Sodium Chloride Injection, Ringer's Solution, or Lactated Ringer's Injection. The formulations may be presented in unit-dose or multi- dose sealed containers, for example, ampoules and vials, and may be stored in a freeze- dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use. Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules, and tablets. Formulations may be in the form of liposomes or other nanoparticulate or microparticulate systems which are designed to target the active compound to blood components or one or more organs.

[0087] 3.3 Transmembrane Formulation

[0088] Transmembrane formulations are those suitable for topical and tansmucosal uses, which include but are not limited to, ophthalmic solutions, sprays, aerosols, creams, lotions, ointments, gels, solutions, suspensions, skin patches and the like. The patches include reservoir type and matrix type skin patches, and may adhere onto the skin for a certain period of time to allow the active component to be adsorbed into the subject's body.

[0089] For topical administration, a wide variety of dermatologically acceptable inert excipients well known to the art may be employed. Typical inert excipients may be, for example, water, ethyl alcohol, polyvinyl pyrrolidone, propylene glycol, mineral oil, stearyl alcohol and gel-producing substances. All of the above dosages forms and excipients are well known to the pharmaceutical art. The choice of the dosage form is not critical to the efficacy of the composition described herein.

[0090] For transmucosal administration, the agent of the present disclosure may also be formulated in a variety of dosage forms for mucosal application, such as buccal and/or sublingual drug dosage units for drug delivery through oral mucosal membranes. A wide variety of biodegradable polymeric excipients may be used that are pharmaceutically acceptable, provide both a suitable degree of adhesion and the desired drug release profile, and are compatible with the active agents to be administered and any other components that may be present in the buccal and/or sublingual drug dosage units. Generally, the polymeric excipient comprises hydrophilic polymers that adhere to the wet surface of the oral mucosa. Examples of polymeric excipients include, but are not limited to, acrylic acid polymers and copolymers; hydrolyzed polyvinyl alcohol; polyethylene oxides; polyacrylates; vinyl polymers and copolymers; polyvinylpyrrolidone; dextran; guar gum; pectins; starches; and cellulosic polymers. In certain embodiments, the agent of the present disclosure may also be formulated in a dosage form for inhalation through nose or mouth, a solution or suspension containing the agent of the present disclosure and a pharmaceutical excipient generally accepted for this purpose is inhaled through an inhalant aerosol spray. Alternatively, the agent of the present disclosure in the form of a powder may be administered through inhalator that allows direct contact of the powder with the lung. To these formulations, if necessary, pharmaceutical acceptable carriers such as isotonic agents, preservatives, dispersions, or stabilizers may be added. Further, if necessary, these formulations may be sterilized by filtration, or by treatment with heat or irradiation.

[0091] The following examples illustrate the invention. [0092] EXAMPLES [0093] Materials and Methods [0094] Cell Culture

[0095] African green monkey kidney Vero E6 cells were grown in Minimum essential medium (Eagle) in Earle's BSS supplemented with 10% FBS, 2 mM 1-glutamine, 1 mM pyruvate, 0.1 mM non-essential amino acids and 1.5 g/L sodium bicarbonate at 37°C in the presence of 5% CO ₂ atmosphere.

[0096] Compound Library [0097] 1. Known compounds [0098] A total of 2,855 unique molecules or chemical entities, approved and clinically- evaluated drugs were gathered for the anti-viral screening in this study. These compounds were dissolved in DMSO at a concentration of 1 mM and transferred to 96- well microtiter plates for the antiviral activity assay based on the prevention of the SARS- CoV-2-mediated cytopathic effect. [0099] 2. Preparation of Nefinavir derivatives (Bn)

[0100] Nelfinavir derivative (Bn) were synthesized in accordance with the procedures described in Scheme 1.

[0101] Scheme 1. Synthesis of Nefinavir derivative (Bn)

[0102] Nelfinavir derivative (N-Bn) 'H NMR (600 MHz, CD ₃ OD): d 7.42 (d, J =7.7 Hz, 2H, Ar-H), 7.22-7.17 (m, 4H, Ar-H), 7.15-7.08 (m, 4H, Ar-H), 6.92 (t, J= 7.7

Hz, 1H, Ar-H), 6.81 (d, J= 7.5 Hz, 1H, Ar-H), 6.72 (d, J = 7.4 Hz, 1H, Ar-H), 4.32 (m, 1H), 4.09 (dd, J= 22.0, 14.9 Hz, 2H), 3.96 (m, 1H), 3.45 (dd, J= 13.7, 4.2 Hz, 1H), 3.18 (dd, J= 13.7, 10.3 Hz, 1H), 2.98 (dd, J= 11.7, 2.4 Hz, 1H), 2.64 (dd, J= 10.9, 3.0 Hz, 1H), 2.56 (dd, J= 12.7, 8.6 Hz, 1H), 2.19 (s, 3H, Ar-CH ₃ ), 2.13-2.05 (m, 2H), 1.96 (q, J = 12.6 Hz, 1H), 1.72-1.62 (m, 2H), 1.58-1.51 (m, 2H), 1.49-1.39 (m,2H), 1.33-1.20 (m,

4H), 1.17-1.08 (m, 1H); ¹³ C NMR (150 MHz, CD3OD): d = 177.0, 173.8, 157.3, 140.2, 137.9, 131.2, 130.3, 129.8, 128.9, 128.5, 127.6, 127.4, 123.7, 119.6, 117.1, 71.3, 70.9, 60.3, 60.2, 54.2, 43.9, 37.6, 35.4, 32.3, 31.8, 27.6, 27.3, 22.2, 13.5; HRMS (ESI-TOF) m/e : Calcd for C35H44N3O4S [M+H]+: 602.3053 Found 602.3047. [0103] 3. Herbal Extracts

[0104] About 200 herbal medicines and supplements were collected by the following procedure. Dissolving 1.0 gram of the ground herbal medicine in water (20 mL) for 4 hours and the mixture was centrifuged to collect the supernatant. Then, 100 μL of the supernatant was combined with 100 μL of the DMEM medium, and the mixture was applied to further assay (e.g., Cytotoxicity assay).

[0105] 4. Reishi Fraction 3 of Ganoderma lucidum

[0106] Reishi glycoprotein raw materials were obtained from Wyntek and fractionated as previously described (S. F. Kiao et al., Proc. Natl. Acad. Sci. U. S. A. 110, 13809- 13814 (2013)). [0107] 5. Preparation of Soho Tea

[0108] Soho Tea was prepared by extracting a total of 11.0 grams of herbs in 350 mL hot water for 20 min in accordance with the formulations described in Table 1.

[0109] Table 1 Soho Tea Formulation

Soho Tea # 1 Soho Tea #2

[0110] Primary screening for identification of anti-SARS-CoV-2 compounds.

[0111] Compounds from the library prepared as 1 mM solutions in DMSO were transferred into 96-well plates. All compounds were diluted in DMEM (2% FBS) to final concentrations of 10, 3.3, and 1 mM (or lower cone, for potent compounds) for screening. Herbal extracts (1.0 g/20 mL H ₂ O) and Reishi extracts (0.25 mg/mL) were 2-fold serial diluted in DMEM (2% FBS) for screening. Vero E6 cells (1 x 10 ⁴ per well) were cultured in a 96-well plate in DMEM supplemented with 10% FBS. The culture medium was removed after a 1-day incubation, when the cells reached 80-90% confluence. A solution of 100 mE of DMEM, with 2% FBS containing the compound to be tested, was placed in each of three wells. Cells were incubated in a CO ₂ incubator at 37°C with SARS-CoV-2 (hCoV-19/Taiwan/NTU04/2020, isolated from the throat swab of a confirmed 39 y/o male patient from Taiwan) at a dose of 100 TCID50 per well; the cytopathic morphology of the cells was examined by using an inverted microscope at 72 h and 120 h. [0112] Cytotoxicity study

[0113] The cytotoxicity of compound to the Vero E6 cells was assayed using the CCK- 8 cell counting kit (Dojindo Labortories) according to the manufacturer’s protocol. Briefly, after incubation with the indicated compounds at various concentrations for 24 h, 10 μL of the CCK-8 reagent were added to each well of the 96-well plate and placed in a CO ₂ incubator for 1 to 4 h to react. The absorbance was measured with a spectrophotometer (SpectraMax M2, Molecular Devices) at 450 nm. Data are expressed as percentage of control cells (as 100%) cultured in the absence of compounds.

[0114] 3CL Protease assay

[0115] Nsp5 was incubated with Fluorescein-AVLQSGFRK(QXL520)-NH ₂ in the absence or presence of indicated inhibitors in 20 mM Tris-HCl (pH 7.0) at 30°C for 30 minutes. The reaction was monitored with fluorescence (ex480/em530) with a plate reader and the initial velocity was calculated. The curves were fitted using Prism (Graphpad).

[0116] Animal study [0117] Female Golden Syrian hamsters, aged 5-7 weeks old were used in the present study. 100 μL of PBS containing lxl 0 ⁵ TCID50 of SARS-CoV-2 was intranasal instilled under intraperitoneal anesthesia with Zoletil 50 (5 mg/kg) at day 0, and the mock-infected hamsters were challenged with 100 μL of PBS. Body weight and clinical signs of the hamsters were monitored daily during the study as a measure of disease progression. Treatment groups were given through oral administration twice a day with any one of mefloquine, nelfinavir, salinomycin, or thioguanine at a dose of 30 mg/kg/day, leaves of Perilla frutescens (200 mg/kg/day), leaves of Mentha haplocalyx (200 mg/kg/day), and extract of Ganoderma lucidum (30 mg/kg/day), while the control group was given an equal volume of drinking water. At day-3 post-infection, all the hamsters were euthanized and the lung tissues were harvested for live viral load measurement by TCID50 assay in Vero E6 cells.

[0118] Example 1 Identification and characterization of anti-SARS-CoV-2 compounds

[0119] In this example, compound(s) having the ability to suppress S ARS-CoV -2 were screened from the compound library (which included herbal extracts) constructed in accordance with the procedures described in the "Materials and Methods" section using cell-based assays.

[0120] 1.1 Screening of drugs

[0121] The antiviral activity of a candidate compound was assessed by visualization of the extent of cytopathogenic effect (CPE) on Vero E6 cells when infected with a strain of SARS-CoV-2 at concentrations of 10 pM, 3.3 pM and 1 pM respectively (or in the range from 1 nM to 100 nM for potent compounds). Of the 2,855 compounds tested, 15 were found to exhibit protective effects on Vero E6 cells. The activities of these compounds were evaluated on day-3 and day-5, and the minimal concentrations that showed protective effect are summarized in Table 2, in which the concentration of drugs required to inhibit 50% (IC50) of virus replication along with their 50% cytotoxicity (CC50) are shown.

[0122] Table 2. In vitro anti-SARS-CoV-2 assay.

[0123] It was found that nelfmavir, nelfmavir mesylate, and nelfmavir derivative (Bn) respectively inhibited 3CL main protease with an IC50 of 56 + 15.8 mM, 33.4 + 6.2 mM, and 35 + IImM. [0124] The library used in the screening process also contained several other clinically approved HIV protease inhibitors, including indinavir sulfate, saquinavir mesylate, atazanavir, ritonavir, darunavir, amprenavir, and lopinavir, and the HCV protease inhibitors daclatasvir, danoprevir and telaprevir, however, none of these compounds possessed inhibitory effects against SARS-CoV-2 in the concentrations used in the screening (data not shown).

[0125] In addition, several known viral polymerase inhibitors, including acyclovir, famciclovir, penciclovir, ribavirin, cidofovir and entecavir, and reverse transcriptase inhibitors, including zalcitabine, nevirapine, efavirenz, abacavir sulfate, tenofovir disoproxil fumarate, adefovir dipivoxyl, delavirdine and telbivudine were also screened in the cell-based assay but no active compound was identified (data not shown).

[0126] 1.2 Combinational use

[0127] The effects of nelfinavir (Nel), cepharanthine (Cepha), and ivermectin (Iver), alone or in combination, against SARS-CoV-2 at various doses were also determined. Synergistic or antagonistic interactions for the combinations were analyzed by the median-effect principle. Combination index (CI) was calculated in accordance with equation (I) described below, and the values of <1, 1, and >1 indicated synergism, additive effect, and antagonism, respectively. D ₁ and D ₂ indicated the antiviral EC ₅₀ of each drug after combination, and (Dx)i and (Dx)2 indicated the antiviral EC ₅₀ of each drug treated alone.

[0128] Three drugs including Nel, Cepha, and Iver were combined in the molar ratios of 1:1 in Nel/Iver group, 2:1 in Cepha/Iver group, and 2:1 in Cepha/Nel group, respectively. Results are summarized in Table 3.

[0129] The data in Table 3 indicated that all three combinations exhibited synergistic inhibitory effects against the delta strain, and the Cepha/Iver combination exhibited synergistic inhibition against the alpha strain. Taken together, the results indicated that the combination strategy of these compounds was applicable for the further evaluation in animal models.

[0130] Table 3. In vitro combination index of three compounds against SARS-CoV-2.

[0131] 1.3 Screening of traditional Chinese herbal medicines.

[0132] Some well-known traditional Chinese herbal medicines were also tested in the cell-based assay, in which the medical herbs (1.0 g) were extracted by water (20 mL) at room temperature and diluted with assay buffer, and results are illustrated in FIG 1. [0133] It was found that the aqueous extracts of herbs from Lamiaceae ( Perilla frutescens), Mentheae ( Mentha haplocalyx), Asteraceae ( Taraxacum mongolicum, Tussilago farfara, Chrysanthemum morifolium), Theaceae {Camellia sinensis), Lamiaceae {Prunella vulgaris, Ocimum basilicum, Salvia hispanica, Nepeta tenuifolia, Salvia rosmarinus), Fabaceae {Arachis hypogaea, Spatholobus suberectus ) and Sapindaceae {Dimocarpus longan, Litchi chinensis ) families were capable of reducing the

CPE of SARS-CoV-2 in Vero E6 cells when the extracts were diluted to 16-960 folds. These herbs contain flavonoids e.g., (myricetin), flavan-3-ol (e.g., catechin and epigallocatechin gallate), caffeic acid derivatives (e.g., caftaric acid, rosmarinic acid methyl ester, and chlorogenic acid, however, whether they are related to the antiviral activity remains to be investigated. It was reported that monoterpenes (1, 8-cineole and camphor from basil leaves), diterpenes (camosic acid and patchouli alcohol), and triterpenes (e.g., ursolic acid) were able to block virus entry and replication. However, the exact mechanisms of these Chinese herbal medicines to inhibit the infection of SARS- CoV-2 are still unknown. [0134] Further, several fractions of L-fucose-containing polysaccharides previously isolated and characterized from Ganoderma lucidum (Reishi) were also tested in the cell- based anti-SARS-CoV-2 assay, and the Reishi L-fucose-containing polysaccharides fraction 3 (RF3) was found to exhibit outstanding cell protecting efficacy (2 μg/mL), which was still active at 1,280-fold dilution, with no cytotoxicity (FIG 1).

[0135] Example 2 In vivo Anti-SARS-CoV-2 activity of the compounds or herbal extracts identified in Example 1.

[0136] In this example, the drugs and herbal extracts identified from the cell-based assay in Example 1 were subject to animal study in accordance with the procedures described in "Materials and Methods" section. Specifically, 4 drugs including mefloquine, nelfinavir, salinomycin, and thioguanine; and three active herbal extracts including RF3, Perilla frutescens, and Mentha haplocalyx, were subject to evaluatation of their viral eradicating efficacy in female golden Syrian hamsters. Results are illustrated in FIG 2. [0137] Salinomycin was shown to cause higher weight loss than the control group

(water administrated), while all other drugs and extracts showed insignificant weight loss. Therefore, the issue of acute toxicity was not a concern in the chosen drugs and extracts, except salinomycin. In the animal study, hamsters were infected with SARS-CoV-2 intranasally at day 0, and after three-day treatment of orally administered drugs (at a dose of 30 mg/kg/day) and extracts (200 mg/kg/day) the hamsters were then sacrificed and the lungs were collected for viral load test. Surprisingly, the two compounds, thioguanine and salinomycin, with better cell-based assay activity showed no significant viral eradication effect in the animal study; this unexpected result could be related to the high hydrophilicity with low oral bioavailability of the compounds. However, mefloquine and extract of Mentha haplocalyx significantly reduced viral load than that of control (P

0.005. FIG 2), while nelfinavir, extracts ofRF3, and Perilla frutescens also showed good antiviral effects (P = 0.03 v.s. control, FIG 2). In the in vivo assay, mefloquine and nelfinavir were identified as potential drug-repurposing agents and extracts of Mentha haplocalyx, Perilla frutescens, and RF3 as potential anti-SARS-CoV-2 herbal candidates. [0138] Example 3 In vivo Anti-SARS-CoV-2 activity of Soho tea [0139] In this example, Soho tea prepared in accordance with procedures described in "Materials and Methods" section was given to hamster that had been exposed to SARS- CoV-2 virus as drinking water, and changes in the body weight, lung virus titer were determined. Results are depicted in FIG 3 and Table 4, [0140] After giving Soho tea to hamster as drinking water, the lung virus titer was reduced to a level lower than the detection limit in both virus elimination (FIG 3, (B)) and protection experiments (FIG 3, (C)) without apparent weight loss (FIG 3, (A)), [0141] Comparative studies on the efficacies of two Soho tea formulations (# 1 and #2) against SARS-CoV2 were conducted, in which the SARS-CoV2 infected mice were treated with formulations # 1 and #2 for 6 days, then lung virus titers were determined. Results are summarized in Table 4. It was found that formulation # 2 of the Soho tea conferred a better protective effect over that of the formulation # 1.

[0142] Table 4. Protective effects of Soho tea against SARS-CoV2. [0143] It will be understood that the above description of embodiments is given by way of example only and that various modifications may be made by those with ordinary skill in the art. The above specification, examples, and data provide a complete description of the structure and use of exemplary embodiments of the invention. Although various embodiments of the invention have been described above with a certain degree of particularity, or with reference to one or more individual embodiments, those with ordinary skill in the art could make numerous alterations to the disclosed embodiments without departing from the spirit or scope of this invention.