OF THE RESPIRATORY SYSTEM

Field of the Invention

[0001] Provided herein are compositions comprising a plurality of terpenes and a plurality of terpenoids and uses thereof for preventing viral induced severe acute respiratory syndrome (SARS), reducing the risk of infection, and treating viral infections.

Background of the Invention

[0002] Outbreaks of new and possibly lethal viral-induced diseases, such as, Severe acute respiratory syndrome-related coronavirus (SARSr-CoV), Middle East Respiratory Syndrome (MERS) and the Avian and Swine Influenzas are of main concern worldwide. The continuous and rapid increase in world population, and the open borders, enhance the potential for disease spread at epidemic levels.

[0003] In the 21 ^st century, two viral strains led pandemics of severe respiratory diseases in humans: SARS-CoV, also known as SARS which erupted during the years 2002 and 2003; and SARS-CoV-2, also known as COVID-19, erupted late 2019. The SARSr-CoV family includes many other strains, however, they all known to infect only non-human species.

[0004] Respiratory-system diseases mainly result from inhalation of airborne pathogens. Inhaled airborne pathogens entering the lungs through the nostrils can induce infections in the respiratory system and potentially may cause further damages once entering the blood stream.

[0005] Concern of epidemics lead the authorities around the world to various, at times drastic, preventative procedures, while expecting the scientific community to develop new treatments and new preventive vaccines.

[0006] The motivation of the authorities arises from concern for the well beings of individuals, however, there are also enormous economic interests in preventing epidemics.

[0007] US Patent No. 5,126,376 discloses methods of treating systemic viral infections, including, retroviral infections by parenteral administration of ozonides of terpenes. [0008] US Patent No. 7,048,953 discloses methods for treating, reducing the risk of and/or curing, infections of the respiratory pathogens causing Severe Acute Respiratory Syndrome ("SARS"), by inhalation of concentrated vapors from botanical essential oils from Eucalyptus globulus, Melaleuca alternifolia, Eucalyptus citriodora and Eucalyptus radiata.

[0009] Cinatl et al. (Lancet, 361:2045-2046, 2003) disclose the use of glycyrrhizin for inhibiting replication of the SARS-associated virus.

[0010] Kamin et al. (Phytomedicine, 14: 787-791, 2007) disclose the use of a commercial ointment containing Eucalyptus oil, pine needle oil and menthol (Pinimenthol®) for treating respiratory tract infections.

[0011] Wen et al. (J. Med. Chem., 50: 4087-4095, 2007) disclose abietane-type diterpenoids and lignoids compounds exhibiting strong anti-SARS-CoV effects, in vitro.

[0012] Loizzo et al. (Chemistry & Biodiscovery, 5: 461-470, 2007) disclose the antiviral activity, in vitro, of essential oils extracted from Lebanon species, namely, L. nobilis oil and J. oxycedrus ssp. against SARSCoV and HSV-1, respectively.

[0013] Horvath et al. (DOI 10.1002/ffj.3252; 2015) is a review of essential oils for the treatment of respiratory tract diseases.

[0014] There is an immediate need for more effective compositions for preventing, reducing the risk of, and treating viral induced severe acute respiratory syndrome (SARS).

Summary of The Invention

[0015] There are provided unique compositions comprising a combination of terpenes and terpenoids. Further provided are methods preventing viral induced severe acute respiratory syndrome (SARS), reducing the risk of infection, and treating viral infections by passive or active inhalation of the compositions disclosed herein.

[0016] Advantageously, the compositions disclosed herein comprise terpenes and terpenoids that exhibit a dual therapeutic effect, namely, anti- viral and anti-inflammatory. Thus, use of the compositions disclosed herein for treating viral infection associated with inflammation, is particularly beneficial. To this end, each of the terpenes and terpenoids included in the compositions disclosed herein was carefully selected from numerous terpenes and terpenoids known in the art, such that the selected terpenes and terpenoids are those having the ability to exert a meaningful anti-viral and anti-inflammatory therapeutic effects. Another advantage conferred by the compositions disclosed herein is that they include volatile components which easily spread throughout the respiratory system. Accordingly, treatment provided by inhalation of the compositions disclosed herein is highly beneficial, adequate and effective for treating infectious disease that attack the respiratory system, including, but not limited to, diseases and infections associated with COVID-19.

[0017] According to some embodiments, there is provided an antiviral composition comprising at least three terpenes and terpenoids.

[0018] According to some embodiments, the at least three terpenes comprise a plurality of sesquiterpenes and a plurality of monoterpenes.

[0019] According to some embodiments, the at least three terpenoids comprise a plurality of monoterpenoids.

[0020] According to some embodiments, the antiviral composition comprises at least four terpenes and terpenoids. According to some embodiments, the antiviral composition comprises at least five terpenes and terpenoids.

[0021] According to some embodiments, the plurality of sesquiterpene comprises at least two sesquiterpene selected from the group consisting of alpha caryophyllene, beta caryophyllene, caryophyllene oxide and santalol.

[0022] According to some embodiments, the plurality of monoterpenes comprises at least two monoterpene selected from the group consisting of alpha phellandrene, alpha terpinene, alpha pinene, beta pinene, gamma terpinene, limonene, menthol and sabinene.

[0023] According to some embodiments, wherein the at least three terpenes and terpenoids are selected from the group consisting of glycyrrhizic acid, alpha pinene, thymol, p-cymene, alpha terpineol, cadinene, citral, 1,8 cineol (eucalyptol), isoborneol, limonene, Citral (lemonal), borneol, caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, beta pinene, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta- hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans- Beta-Ocimene, Linalool and forskolin.

[0024] According to some embodiments, the antiviral composition further comprises at least one additional compound selected from CBD and essential oils.

[0025] According to some embodiments, the antiviral composition further comprises CBD.

[0026] According to some embodiments, the antiviral composition in a form suitable for inhalation. According to some embodiments, the form suitable for inhalation is selected from the group consisting of nose drops, nasal sprays, sprayable liquid composition, inhalants and throat sprays.

[0027] According to some embodiments, the antiviral composition is in a form suitable for topical application. According to some embodiments, the form suitable for topical application is selected from the group consisting of liquid, creams, balms, gels, embedded within wipes, or embedded within tissue papers liquid, creams, balms, gels, embedded within wipes, or embedded within tissue papers.

[0028] According to some embodiments, there is provided a pressurized aerosol dosage form comprising the antiviral composition disclosed herein. According to some embodiments, the pressurized aerosol dosage form is encapsulated in a cartridge or a capsule.

[0029] According to some embodiments, a device comprising the antiviral composition disclosed herein, the device is selected from the group consisting of a respiratory machine, a mechanical ventilator, a life support device, a face mask connected to oxygen source and a face mask.

[0030] According to some embodiments, there is provided a device comprising a pressurized aerosol dosage form comprising the antiviral composition disclosed herein, wherein the device is configured to produce aerosol from said pressurized aerosol dosage form. According to some embodiments, the device is selected from the group consisting of nebulizer, MESH ultrasonic nebulizer, inhaler and atomizer. According to some embodiments, said device is a hand-held device.

[0031] According to some embodiments, there is provided a method of treating an infection of the human respiratory system induced by a Severe Acute Respiratory Syndrome -related coronavirus (SARSr-CoV) in a human subject in need thereof, the method comprising administering to the human subject a pharmaceutically effective amount of the antiviral composition disclosed herein.

[0032] According to some embodiments, said administering is via inhalation. According to some embodiments, said administering via inhalation comprises administering via an apparatus configured to produce vapor and/or aerosol.

[0033] According to some embodiments, said treating comprises at least one of inhibiting the progression of the infection, inhibiting the activity of SARSr-CoV, suppressing the activity of SARSr-CoV, preventing the progression of the infection, reliving bronchial congestion and assisting in opening clogged sinus passages.

[0034] According to some embodiments, the SARSr-CoV is COVID-19.

[0035] According to some embodiments, the subject in need thereof is a subject diagnosed with infection of the respiratory system induced by SARSr-CoV.

[0036] According to some embodiments, the method further comprises co-administering at least one additional therapeutic agent.

[0037] According to some embodiments, there is provided a method for reducing the risks of infection of the human respiratory system of at least one human in an enclosed area, wherein the infection is induced by SARSr-CoV, the method comprising enriching the environment of the enclosed area with the antiviral composition disclosed herein.

[0038] According to some embodiments, the enclosed area is an enclosed private area. According to some embodiments, the enclosed area is a private residential property.

[0039] According to some embodiments, the enclosed area is having a ventilation system and said enriching the environment of the enclosed area comprises providing, through the ventilation system of the enclosed area, the antiviral composition.

[0040] According to some embodiments, the ventilation system is an air-conditioning system.

[0041] According to some embodiments, said enclosed area is having at least one diffuser and said enriching the environment of the enclosed area comprises providing, through the at least one diffuser, the pharmaceutical composition. According to some embodiments, the diffuser is configured to release said pharmaceutical composition, automatically, at predetermined time periods.

[0042] According to some embodiments, there is provided an antiviral composition as disclosed herein, in a pharmaceutically effective amount for the treatment of an infection of the human respiratory system induced by a Severe Acute Respiratory Syndrome -related coronavirus (SARSr-CoV). According to some embodiments, the antiviral composition is for use via inhalation.

[0043] Other objects, features and advantages of the present invention will become clear from the following description, examples and drawings.

Brief Description of The Drawings

[0044] Some embodiments of the disclosure are described herein with reference to the accompanying figures. The description, together with the figures, makes apparent to a person having ordinary skill in the art how some embodiments may be practiced. The figures are for the purpose of illustrative description and no attempt is made to show structural details of an embodiment in more detail than is necessary for a fundamental understanding of the disclosure. For the sake of clarity, some objects depicted in the figures are not to scale.

[0045] In the Figures:

[0046] Figure 1 presents cell viability of human lung fibroblasts MRC-5 cells incubated with various concentrations of cannabidiol (CBD), test compound NT-VRL-1 (Table 1), a combination of CBD and NT-VRL-1, positive controls (Pyrazofurin and Glycyrrhizin) and culture medium (untreated cells).

[0047] Figures 2A to 2N are representative images of untreated MRC-5 cells (2A), untreated MRC-5 cells exposed to corona virus (2B), and MRC-5 cell treated with NT-VRL-1 2 pg/ml (2C), NT-VRL-1 5 mg/ml (2D), NT-VRL-1 10 mg/ml (2E), NT-VRL-1 10 mg/ml + CBD 1 mg/ml (2F), NT-VRL-3 5 mg/ml (2G), NT-VRL-3 10 mg/ml (2H mg/ml), NT-VRL-320 mg/ml (21), NT-VRL-1 20 mg/ml + CBD 1 mg/ml (2J), Glycyrrhizin 400 mg/ml (2K), Pyrazofurin 5 mg/ml (2L), CBD 0.5 mg/ml (2M) and CBD 1 mg/ml (2N).

[0048] Figure 3 presents cell viability of human lung fibroblasts MRC-5 cells incubated with various concentrations of CBD, test compound NT-VRL-1 (Table 1), a combination of CBD and NT-VRL-1, NT-VRL-3 (Table 1), a combination of CBD and NT-VRL-3, positive controls (Pyrazofurin and Glycyrrhizin), negative control (cells treated with the virus in the absence of tested compound - untreated cells) and cells in culture medium devoid of the virus and the tested compounds (no virus). Results represent mean percent viability +SEM. Statistics are presented for each treatment compared to cells infected by the virus but not treated with any of the tested compounds (untreated), *p<0.05, **p<0.01, ***p<0.001, according to t-Test.

[0049] Figures 4A to 4N are representative images of untreated MRC-5 cells (4A), untreated MRC-5 cells exposed to corona virus (4B), and MRC-5 cell treated with corona virus pre-incubated with NT-VRL-1 2 mg/ml (4C), NT-VRL-1 5 mg/ml (4D), NT-VRL-1 10 mg/ml (4E), NT-VRL-1 10 mg/ml + CBD 1 mg/ml (4F), NT-VRL-3 5 mg/ml (4G), NT-VRL-3 10 mg/ml (4H mg/ml), NT-VRL-3 20 mg/ml (41), NT-VRL-1 20 mg/ml + CBD 1 mg/ml (4J), Glycyrrhizin 400 mg/ml (4K), Pyrazofurin 5 mg/ml (4L), CBD 0.5 mg/ml (4M) and CBD 1 mg/ml (4N).

[0050] Figure 5 presents cell viability of human lung fibroblasts MRC-5 cells treated with test compounds incubated with the corona virus, prior to being incubated with the cells, where the test compounds were provided at various concentrations of CBD, test compound NT-VRL- 1 (Table 1), a combination of CBD and NT-VRL-1, NT-VRL-3 (Table 1), a combination of CBD and NT-VRL-3, positive controls (Pyrazofurin and Glycyrrhizin), negative control (cells treated with the virus in the absence of tested compound - untreated cells) and cells in culture medium devoid of the virus and the tested compounds (no virus). Results represent mean percent viability +SEM. Statistics are presented for each treatment compared to cells infected by the virus but not treated with any of the tested compounds (untreated), *p<0.05, **p<0.01, ***p<0.001, according to t-Test.

[0051] Figures 6A to 6N are representative images of untreated MRC-5 cells (6A), untreated MRC-5 cells exposed to corona virus (6B), and MRC-5 cell exposed to corona virus and to treatment with NT-VRL-1 2 mg/ml (6C), NT-VRL-1 5 mg/ml (6D), NT-VRL-1 10 mg/ml (6E), NT-VRL-1 10 mg/ml + CBD 1 pg/ml (6F), NT-VRL-3 5 mg/ml (6G), NT-VRL-3 10 mg/ml (6H mg/ml), NT-VRL-3 20 mg/ml (61), NT-VRL-1 20 mg/ml + CBD 1 pg/ml (6J), Glycyrrhizin 400 mg/ml (6K), Pyrazofurin 5 mg/ml (6L), CBD 0.5 mg/ml (6M) and CBD 1 mg/ml (6N). [0052] Figure 7 presents cell viability of human lung fibroblasts MRC-5 cells exposed to corona virus and then treated with test compounds) where the test compounds were provided at various concentrations of CBD, test compound NT-VRL-1 (Table 1), a combination of CBD and NT-VRL-1, NT-VRL-3 (Table 1), a combination of CBD and NT-VRL-3, positive controls (Pyrazofurin and Glycyrrhizin), negative control (cells treated with the virus in the absence of tested compound - untreated cells) and cells in culture medium devoid of the virus and the tested compounds (no virus). Results represent mean percent viability +SEM. Statistics are presented for each treatment compared to cells infected by the virus but not treated with any of the tested compounds (untreated), *p<0.05, **p<0.01, ***p<0.001, according to t-Test.

[0053] Figure 8 presents AlamarBlue® viability assay presented as percentage of viable primary human PBMCs out of NT (No Treatment) negative control for various concentrations of test compound FI (NT-VRL-1; Table 1) and F2 (NT-VRL-2; Table 1).

[0054] Figures 9 A to 9D present the effect of the test compositions on LPS -induced pro- inflammatory cytokine secretion by human PBMCs derived from a first donor, for the cytokines IL-bI, TNF-oc, IL-6 and IL-8, respectively.

[0055] Figures 10A to 10D present the effect of the test compositions on LPS -induced pro- inflammatory cytokine secretion by human PBMCs derived from a second donor, for the cytokines IL-bI, TNF-oc, IL-6 and IL-8, respectively.

Detailed Description

[0056] Provided herein are compositions comprising at least three terpenes and/orterpenoids. Further provided are methods preventing viral induced severe acute respiratory syndrome (SARS), reducing the risk of infection, and treating viral infections by passive or active inhalation of the compositions disclosed herein.

[0057] In some embodiments, there is provided a composition comprising at least three terpenes and/or at least three terpenoids. In some embodiments, there is provided a composition comprising at least three terpenes and at least three terpenoids.

[0058] Terpenes are natural, volatile compounds, that contain only carbon, hydrogen and oxygen atoms primarily extracted from plants. The physiological roles of terpenes in plants include chemoattractants or chemorepellents. Terpenes are largely responsible for the plant fragrance. In animals and humans, terpenes display diverse pharmacological functionalities including anti inflammation, analgesia, anti-microbial as well as antiviral properties.

[0059] Terpenoids are modified class of terpenes with different functional groups and oxidized methyl group moved or removed at various positions.

[0060] According to some embodiments, terpenes and terpenoids are interchangeable.

[0061] A wide range of in vitro studies have shown the antiviral potential of terpenes against a wide range of viruses such as herpes simplex virus, Bronchitis Virus, West Nile virus and HIV-1.

[0062] Terpenes have been shown to have antiviral effectivity against several types of HCoVs. Glycyrrhizin, a triterpene naturally occurring in licorice roots, was one of the first compounds found to be active against SARS Coronavirus (SARS-CoV) in vitro where it was shown to inhibit SARS-CoV replication with an EC50 of 365 mM. In addition, Glycyrrhizin was used as treatment of SARS patients which displayed positive results on its efficacy to fight the virus. L. nobilis essential oil, with beta-ocimene, 1,8-cineole, alpha-pinene, and beta-pinene as the main constituents, exert an antiviral activity against SARS-CoV with an IC50 value of 120 mg/ml.

[0063] In some embodiments, the at least three terpenes comprise a plurality of sesquiterpenes and a plurality of monoterpenes. In some embodiments, the at least three terpenoids comprise a plurality of monoterpenoids.

[0064] In some embodiments, the composition comprises at least four terpenes. In some embodiments, the composition comprises at least five terpenes. In some embodiments, the composition comprises at least six terpenes. In some embodiments, the composition comprises at least seven terpenes. In some embodiments, the composition comprises at least eight terpenes. In some embodiments, the composition comprises at least nine terpenes. In some embodiments, the composition comprises at least ten terpenes. In some embodiments, the composition comprises at least 11 terpenes. In some embodiments, the composition comprises at least 12 terpenes.

[0065] In some embodiments, the composition comprises at least four terpenoids. In some embodiments, the composition comprises at least five terpenoids. In some embodiments, the composition comprises at least six terpenoids. In some embodiments, the composition comprises at least seven terpenoids. In some embodiments, the composition comprises at least eight terpenoids. In some embodiments, the composition comprises at least nine terpenoids. In some embodiments, the composition comprises at least ten terpenoids. In some embodiments, the composition comprises at least 11 terpenoids. In some embodiments, the composition comprises at least 12 terpenoids.

[0066] In some embodiments, the at least three terpenes and at least three terpenoids are selected from the group consisting of: glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta, 12-diacetoxyabieta-6, 8, 11,13- tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxy deoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0067] According to some embodiments, the at least three terpenes and/or terpenoids comprises glycyrrhizic acid and/or glycyrrhizin and further comprise a plurality of compounds selected from the group consisting of alpha pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, carvacrol, beta pinene, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta-hydroxyabieta- 9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxy deoxycryptojaponol, trans-beta- ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0068] According to some embodiments, the at least three terpenes and/or terpenoids comprises alpha pinene and/or beta pinene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, carvacrol, beta pinene, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta-hydroxyabieta- 9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxy deoxycryptojaponol, trans-beta- ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0069] According to some embodiments, the at least three terpenes and/or terpenoids comprises thymol and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxy deoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0070] According to some embodiments, the at least three terpenes and/or terpenoids comprises p-cymene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, carvacrol, beta pinene, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxy deoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0071] According to some embodiments, the at least three terpenes and/or terpenoids comprises alpha terpineol and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0072] According to some embodiments, the at least three terpenes and/or terpenoids comprises cadinene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0073] According to some embodiments, the at least three terpenes and/or terpenoids comprises citral and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, borneol, caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0074] According to some embodiments, the at least three terpenes and/or terpenoids comprises 1,8 cineol (eucalyptol) and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0075] According to some embodiments, the at least three terpenes and/or terpenoids comprises at least one of isoborneol and borneol and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p- cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), limonene, citral (lemonal), caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0076] According to some embodiments, the at least three terpenes and/or terpenoids comprises limonene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, citral (lemonal), borneol, caryophyllene oxide, alpha terpinene, gamma terpinene, camphor, santalol, beta caryophyllene, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, alpha caryophyllene (alpha humulene), ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0077] According to some embodiments, the at least three terpenes and/or terpenoids comprises at least one of caryophyllene oxide, alpha caryophyllene and beta caryophyllene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta, 12- diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention. [0078] According to some embodiments, the at least three terpenes and/or terpenoids comprises at least one of alpha terpinene and gamma terpinene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0079] According to some embodiments, the at least three terpenes and/or terpenoids comprises at least one of trans-beta-ocimene and trans-beta-ocimene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, camphor, santalol, menthol, carvone, carvacrol, myrcene, alpha terpinene or gamma terpinene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0080] According to some embodiments, the at least three terpenes and/or terpenoids comprises camphor and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien- 12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0081] According to some embodiments, the at least three terpenes and/or terpenoids comprises santalol and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien- 12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0082] According to some embodiments, the at least three terpenes and/or terpenoids comprises menthol and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien- 12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0083] According to some embodiments, the at least three terpenes and/or terpenoids comprises carvone or carvacrol and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0084] According to some embodiments, the at least three terpenes and/or terpenoids comprises myrcene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien- 12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, Trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0085] According to some embodiments, the at least three terpenes and/or terpenoids comprises sabinene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien- 12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0086] According to some embodiments, the at least three terpenes and/or terpenoids comprises alpha phellandrene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, betulonic acid, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0087] According to some embodiments, the at least three terpenes and/or terpenoids comprises betulonic acid, and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, ferruginol, 8 beta-hydroxyabieta-9(ll),13-dien-12- one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0088] According to some embodiments, the at least three terpenes and/or terpenoids comprises ferruginol, and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, 8 beta-hydroxyabieta-9(ll),13-dien-12- one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0089] According to some embodiments, the at least three terpenes and/or terpenoids comprises savinin, and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta- 9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxydeoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0090] According to some embodiments, the at least three terpenes and/or terpenoids comprises dehydroabieta-7-one and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta- 9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, 7 beta-hydroxydeoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0091] According to some embodiments, the at least three terpenes and/or terpenoids comprises 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta- hydroxyabieta-9(ll),13-dien-12-one, savinin, curcumin, pinusolidic acid, dehydroabieta-7- one, 7 beta-hydroxydeoxycryptojaponol, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0092] According to some embodiments, the at least three terpenes and/or terpenoids comprises 7 beta-hydroxy deoxy cryptojaponol and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p- cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta- hydroxyabieta-9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, trans-beta-ocimene, linalool and forskolin. Each possibility is a separate embodiment of the present invention.

[0093] According to some embodiments, the at least three terpenes and/or terpenoids comprises linalool and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta- 9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxy deoxy cryptojaponol, trans-beta- ocimene and forskolin. Each possibility is a separate embodiment of the present invention. [0094] According to some embodiments, the at least three terpenes and/or terpenoids comprises forskolin and a plurality of compounds selected from the group consisting of glycyrrhizic acid, glycyrrhizin, alpha pinene, beta pinene, thymol, p-cymene, alpha terpineol, cadinene, 1,8 cineol (eucalyptol), isoborneol, limonene, citral (lemonal), borneol, caryophyllene oxide, alpha caryophyllene (alpha humulene), beta caryophyllene, alpha terpinene, gamma terpinene, camphor, santalol, menthol, carvone, carvacrol, myrcene, ocimene, sabinene, alpha phellandrene, betulonic acid, ferruginol, 8 beta-hydroxyabieta- 9(ll),13-dien-12-one, 3 beta,12-diacetoxyabieta-6,8,ll,13-tetraene, savinin, curcumin, pinusolidic acid, dehydroabieta-7-one, 7 beta-hydroxy deoxycryptojaponol, trans-beta- ocimene and linalool. Each possibility is a separate embodiment of the present invention.

[0095] In some embodiment, the composition is an antiviral composition. In some embodiments, the composition is a pharmaceutical composition. In some embodiments, the antiviral composition is a pharmaceutical composition.

[0096] The terms "pharmaceutical composition" and "antiviral composition" as used herein are interchangeable and collectively refer to the compositions and formulations disclosed herein. Moreover, in the context of the present disclosure the antiviral agents and antiviral compositions disclosed herein are also anti-inflammatory agents and anti-inflammatory compositions, respectively.

[0097] In some embodiments, any one or more of the aforementioned terpenes and terpenoids may be provided as the derivative or salt thereof. In some embodiments, any one or more of the aforementioned terpenes and terpenoids in the composition is provided as a therapeutically effective derivative or salt. In some embodiments, any one or more of the aforementioned terpenes and terpenoids in the composition is provided as a therapeutically effective derivative or salt. In some embodiments, any one or more of the aforementioned terpenes and terpenoids in the composition is provided as a pharmaceutically acceptable salt. In some embodiments, any one or more of the aforementioned terpenes and terpenoids in the composition is provided as a prodrug.

[0098] By the term "therapeutically effective derivative" it is meant that a chemical derivative of the antiviral agent is a physiologically functional derivative, namely, is having the same physiological/therapeutic function as the original compound. For example, a chemical derivative may be a molecule comprising a modified form of the antiviral agent, such as a pro- drug, which is being convertible in the body into the antiviral agent. Esters, amides and carbamates are examples of physiologically functional derivatives.

[0099] "Pharmaceutically acceptable salt" used herein belongs to a derivative of the antiviral agent which is modified by forming a salt with an acid or a base. Examples of the pharmaceutically acceptable salt include, but are not limited to, an inorganic acid or organic acid salt of a basic moiety such as amine, an alkali metal salt or an organic salt of an acidic moiety such as carboxylic acid, and the like. The pharmaceutically acceptable salt includes conventional non-toxic salt or quaternary ammonium salt of the parent compound, such as a salt formed by a non-toxic inorganic acid or an organic acid. The conventional non-toxic salt includes, but is not limited to, the salt derived from an inorganic acid or an organic acid, wherein the inorganic acid or organic acid is selected from the group consisting of 2- acetoxybenzoic acid, 2-hydroxyethanesulfonic acid, acetic acid, ascorbic acid, benzenesulfonic acid, benzoic acid, bicarbonate, carbonic acid, citric acid, edetic acid, ethanedisulfonic acid, ethanesulfonic acid, fumaric acid, glucoheptose, gluconic acid, glutamic acid, glycolic acid, hydrobromic acid, hydrochloric acid, hydroiodide, hydroxyl, hydroxynaphthalene, isethionic acid, lactic acid, lactose, dodecyl sulfonic acid, maleic acid, malic acid, mandelic acid, methanesulfonic acid, nitric acid, oxalic acid, pamoic acid, pantothenic acid, phenylacetic acid, phosphoric acid, polygalactanal acid, propionic acid, salicylic acid, stearic acid, subacetic acid, succinic acid, sulfamic acid, sulfanilic acid, sulfuric acid, tannin, tartaric acid and p- toluenesulfonic acid.

[00100] As used herein, the term "prodrug" refers to a derivative of an antiviral agent that can hydrolyze, oxidize, or otherwise react under biological conditions (in vitro or in vivo) to provide the antiviral agent. Prodrugs may only become active upon some reaction under biological conditions, but they may have activity in their unreacted forms. Examples of prodrugs contemplated herein include, without limitation, analogs or derivatives of the antiviral agents disclosed herein. Examples of prodrug moieties include substituted and unsubstituted, branch or unbranched lower alkyl ester moieties, (e.g., propionoic acid esters), lower alkenyl esters, di-lower alkyl-amino lower-alkyl esters (e.g., dimethylaminoethyl ester), acylamino lower alkyl esters (e.g., acetyloxymethyl ester), acyloxy lower alkyl esters (e.g., pivaloyloxymethyl ester), aryl esters (phenyl ester), aryl-lower alkyl esters (e.g., benzyl ester), substituted (e.g., with methyl, halo, or methoxy substituents) aryl and aryl-lower alkyl esters, amides, lower-alkyl amides, di-lower alkyl amides, and hydroxy amides. [00101] The antiviral composition may contain from about 0.01% to about 99.99% active ingredient, namely at least three terpenes and/or at least three terpenoids, by weight, from about 0.05% to 99.99% active ingredient, by weight, or from about 0.1 % to 99.99% active ingredient. Each possibility is a separate embodiment of the present invention.

[00102] As used herein the term "about" refers to the designated value ± 10%.

[00103] In some embodiments, the carrier is a pharmaceutically acceptable carrier.

[00104] As used herein the term "pharmaceutically acceptable carrier" is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically and therapeutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compounds, use thereof in the compositions is contemplated.

[00105] In some embodiments, the antiviral composition further includes any one or more of the following ingredients: CBD, lauric acid; simmondsia chinensis; d-limonene; citrus oil (e.g., orange oil, lemon oil, grapefruit oil, tangerine oil, mandarin oil, lime oil, bergamot oil, and petitgrain essential oil); meadowfoam seed oil; soy oil; emu oil; grapefruit seed extract; glycine soja; chlorhexidine gluconate; ginger oil; lavender oil; peppermint oil; spearmint oil; aloe oil; and a preservative such as sodium benzoate, benzalkonium chloride, BHT, vitamin E. Each possibility is a separate embodiment of the present invention.

[00106] In some embodiments, the antiviral composition further includes CBD.

[00107] In some embodiments, the antiviral composition is combined with CBD oil.

[00108] The antiviral compositions disclosed herein may include additionally, or alternatively, pharmaceutically acceptable ingredients added thereto to improve efficacy, stability, usability and/or to facilitate processing, packaging and end-use applications. Inert ingredients may include at least one of carrier, stabilization agent, or physical property modifying agent, which may be added individually or in combination. In some embodiments, the carrier may be a liquid material, such as, water, oil, and other organic or inorganic solvents. In some embodiments, the carrier may be a solid material, selected from minerals, polymers and polymer complexes. The stabilization agent may include anti-caking agents, anti-oxidation agents, desiccants, protectants or preservatives. The physical property modifying agent may include bulking agents, wetting agents, thickeners, pH modifiers, rheology modifiers, dispersants, adjuvants, surfactants, antifreeze agents or colorants. Each possibility is a separate embodiment of the present invention.

[00109] In some embodiments, the antiviral compositions disclosed herein further comprises at least one additional therapeutic agent. In some embodiments, the at least one additional therapeutic agent comprises one or more essential oils.

[00110] In some embodiments, the one or more essential oil includes, but is not limited to, agar oil or oodh, distilled from agarwood (Aquilaria malaccensis), Ajwain oil, distilled from the leaves of (Carum copticum), Angelica root oil, distilled from the Angelica archangelica, Anise oil, from the Pimpinella anisum, Asafoetida oil, Balsam of Peru, from the Myroxylon, Basil oil, Bay oil, Bergamot oil, Black pepper oil, Buchu oil, made from the buchu shrub, Birch oil, Camphor oil, Cannabis flower essential oil, Calamodin oil (or calamansi essential oil), Caraway seed oil, Cardamom seed oil, Carrot seed oil, Cedar oil (or cedarwood oil), Chamomile oil, Calamus oil, Cinnamon oil, Cistus ladanifer oil (leaves and flowers), Citron oil, Citronella oil, Clary Sage oil, Coconut oil, Clove oil, coffee oil, Coriander oil, Costmary oil (bible leaf oil), Costus root oil, Cranberry seed oil, Cubeb oil, Cumin seed oil/black seed oil, Cypress oil, Cypriol oil, Curry leaf oil, Davana oil, from the Artemisia pallens, Dill oil, Elecampane oil, Eucalyptus oil, Fennel seed oil, Fenugreek oil, Frankincense oil, Galangal oil, Galbanum oil, Garlic oil distilled from Allium sativum, Geranium oil, Ginger oil, Goldenrod oil, Grapefruit oil, Henna oil, Helichrysum oil, Hickory nut oil, Horseradish oil, Hyssop, Idaho- grown Tansy, Jasmine oil, Juniper berry oil, Laurus nobilis oil, Lavender oil, Ledum oil, Lemon oil, Lemongrass oil, Lime, Litsea cubeba oil, Linalool, extract of liquorice root, Mandarin oil, Marjoram oil, Melissa oil, Mentha arvensis oil, Moringa oil, Mountain Savory oil, Mugwort oil, Mustard oil, Myrrh oil, Myrtle, Neem oil, Neroli produced from the blossom of the bitter orange tree, Nutmeg oil, Orange oil, Oregano oil, Orris oil extracted from the roots of the Florentine iris (Iris florentina), Iris germanica and Iris pallida, Palo Santo, Palmarosa Essential oil, Parsley oil, Patchouli oil, Perilla essential oil, Pennyroyal oil, Peppermint oil, Petitgrain, Pine oil, Ravensara, Red Cedar, Roman Chamomile, Rose oil, Rosehip oil, Rosemary oil, Rosewood oil, Sage oil, Sandalwood oil, Sassafras oil, Savory oil, from Satureja species, Schisandra oil, Spearmint oil, Spikenard, Spruce oil, Star anise oil, Tangerine, Tarragon oil, distilled from Artemisia dracunculus, Tea tree oil, Thyme oil, Tsuga oil, Turmeric, Valerian oil, Warionia, Vetiver oil (khus oil), Western red cedar, Wintergreen, Yarrow oil and Ylang-ylang oil. Each possibility is a separate embodiment of the present invention.

[00111] In some embodiments, the one or more essential oil is selected from the group consisting of eucalyptus oil, tea tree oil, rosemary oil, peppermint oil, frankincense oil, oregano oil, thyme oil, bergamot oil, nutmeg oil, cypress oil, geranium oil, cinnamon oil, anise oil, bitter fennel oil. Each possibility is a separate embodiment of the present invention.

[00112] In some embodiments, the antiviral compositions disclosed herein comprises an extract of liquorice root.

[00113] In some embodiments, the additional therapeutic agent comprises one or more terpenes. In some embodiments, the one or more terpene is selected from the group consisting of: limonene, citronella, alpha-carotene, beta-carotene, Vitamin A, linalool, linalyl acetate, squalene, geraniol, alpha-pinene, loganin, cymene, farnesanes, eudesmanes, acoranes, cedranes, chamigranes, caryophy llanes, illudanes, humulenes, himachalenes, longifolanes, perhydroazulenes, quaianes, quaianolides, germacranes, labdane, clerodanes, abietic acid, phyllocladene, giberellins, ophiobolin A, retigeranic acid, gasgardic acid, lanosterol, euphol, oleanane, ursane, lupeol, hydroxyphopanone, lupanes, hopanes, B-selinene, zingibene, camphene, sabinene, ocimene, myrcene, nerol, citral A, citral B, farnesol, bisabolene, phytol and cecropia juvenile hormone. Each possibility is a separate embodiment of the present invention.

[00114] In some embodiments, the antiviral composition is for systemic use such as for intravenous, intramuscular, sublingual or intraperitoneal injection. Each possibility is a separate embodiment of the present invention.

[00115] In some embodiments, the antiviral composition is for local application in the form of liquid, suspension, tinctures (dissolved in alcohol or in water), nose drops or nasal sprays, inhalants, throat sprays, creams, balms, gels, embedded within wipes, or embedded within tissue papers. Each possibility is a separate embodiment of the present invention.

[00116] In some embodiments, the antiviral composition disclosed herein is formulated for topical application. In some embodiments, the antiviral composition is in a dosage form for topical application, selected from liquid, creams, balms, gels, embedded within wipes, or embedded within tissue papers.

[00117] In some embodiments, the antiviral composition disclosed herein is formulated for sublingual administration.

[00118] In some embodiments, the antiviral composition disclosed herein is integrated within a pad for topical application. In some embodiments, the antiviral composition disclosed herein is integrated within a face-mask, and is configured to be inhaled while wearing the face- mask.

[00119] In some embodiments, the antiviral composition is integrated in a device that produces droplets, such as, a hand-held spray applicator allowing to spray the composition over the skin, sublingually, over a face-mask and the like.

[00120] In some embodiments, the antiviral composition is integrated in foods and beverages and hence it is consumed during intake of the foods and beverages. It is to be understood that when the composition is integrated in foods and/or beverages, it is provided in a form suitable for oral absorption.

[00121] In some embodiments, the antiviral composition disclosed herein is formulated for administration by inhalation. Inhalation administration can include an intranasal spray. Various forms suitable for administration by inhalation include aerosols, mists or powders. Pharmaceutical compositions comprising the antiviral composition disclosed herein can be conveniently delivered in the form of an aerosol spray presentation from pressurized packaging or a nebulizer, e.g. with the use of a propellant (e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, or the like).

[00122] In some embodiments, the dosage unit of a pressurized aerosol comprising the antiviral composition disclosed herein is determined by selection of a valve that can meter the dose.

[00123] In some embodiments, there is provided a pressurized aerosol dosage form comprising the antiviral composition disclosed herein. [00124] In some embodiments, the composition is blended within CBD oil and is configured for administration via infusion and or inhalation. The composition blended with CBD oil may be also suitable for oral and sublingual administrations.

[00125] In some embodiments, the pressurized aerosol dosage form is encapsulated in a cartridge or a capsule.

[00126] In some embodiments, the composition disclosed herein is in a form of capsules and cartridges for use within a pressurized delivery system.

[00127] In some embodiments, the antiviral composition disclosed herein can be formulated into liquid compositions sprayable from non-aerosol packaging.

[00128] The term "aerosol" as used herein refers to a suspension of liquid or solid particles in a gas. Typically, the diameter of the droplets (also referred to as particle) is within the range of 10 ⁹ to 10 ^-4 m.

[00129] In some embodiments, there is provided a device comprising the pressurized aerosol dosage form disclosed herein, and configured to produce an aerosol.

[00130] In some embodiments, the device is a hand-held device. In some embodiments, the device is selected from an inhaler, a nebulizer and an atomizer. Each possibility is a separate embodiment of the present invention.

[00131] The term "hand-held" as used herein is exchangeable with the term 'portable'.

[00132] In some embodiments, there is provided a method for treating infection of the human respiratory system induced by a Severe Acute Respiratory Syndrome -related coronavirus (SARSr-CoV) in a human subject in need thereof, the method comprising administering to the human subject a pharmaceutically effective amount of at least one antiviral composition from the compositions disclosed herein.

[00133] Coronaviruses are enveloped, positive-sense single-stranded RNA viruses. They have the largest genomes (26-32 kb) among known RNA viruses, and are phylogenetically divided into four genera (alpha, beta, gamma, delta.), with betacoronaviruses further subdivided into four lineages (A, B, C, D). The family of coronavirus is known to cause severe respiratory illness. Viruses currently known to infect human from the coronavirus family are from the alphacoronavirus and betacoronavirus genera. Additionally, it is believed that the gammacoronavirus and deltacoronavirus genera may infect humans in the future.Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) where aerosol droplets is the main means of transmission.

[00134] As used herein, the term "COVID-19" is interchangeable with the terms "coronavirus ", "SARSr-CoV ", "HCoV-229E", "HCoV-OC43", "HCoV-NL63", "HCoV- HKU1", "SARS-CoV2 ", and further refers to diseases, disorders, and symptoms associated with the COVID-19 infection.

[00135] Coronaviruses infect a wide range of avian and mammalian species, including humans. Of the six known human coronaviruses, four (HCoV-OC43, HCoV-229E, HCoV- HKU1, and HCoV-NL63) circulate annually in humans and generally cause mild respiratory diseases, although severity can be greater in infants, elderly, and the immunocompromised. In contrast, the Middle East respiratory syndrome coronavirus (MERS-CoV) and the severe acute respiratory syndrome coronavirus (SARS-CoV), belonging to betacoronavirus lineages C and B, respectively, are highly pathogenic. Both viruses emerged into the human population from animal reservoirs within the last 15 years and caused outbreaks with high case-fatality rates.

[00136] MERS-CoV was isolated in 2012 from a patient in Saudi Arabia and is still circulating across the Arabian Peninsula. Primary transmission, most likely from camels, is now considered to be the most common route of transmission, and camels are thought to be a secondary or intermediate reservoir for MERS-CoV, with bats serving as the primary reservoir. Human-to-human transmission, especially as a result of close contact between patients and hospital workers within health care settings, is another important route of transmission, and was responsible for an outbreak of MERS-CoV in South Korea. The high pathogenicity and airborne transmissibility of SARS-CoV and MERS-CoV have raised concern about the potential for another coronavirus pandemic.

[00137] COVID- 19 was first identified in Wuhan, Hubei province and quickly spread across over whole China and other 30 countries. Despite intensive research conducted with the aim of identifying practical treatments or any possible medicines, there is as yet no consensus as to any recommended antiviral therapy. It has been confirmed that the immune system played a vital role in defense against SARS-CoV and MERS infection. Immunological changes in patients with SARS, MERS, and influenza, especially changes in peripheral blood T lymphocyte subsets, contribute to understanding of the characteristics, diagnosis, monitoring, prevention, and treatment of the disease.

[00138] The high case-fatality rate, and absence of effective prophylactic or therapeutic measures against coronaviruses have created an urgent need for effective therapeutic agents.

[00139] According to certain embodiments, the coronavirus is one of SARS-CoV-2, MERS- CoV, SARS-CoV, NL63-CoV, 229E-CoV, OC43-CoV, HKUl-CoV, WIVl-CoV, MHV, HKU9-CoV, PEDV-CoV, or SDCV. According to certain embodiments, the coronavirus is SARS-CoV-2.

[00140] The term 'infection' as used herein is interchangeable with the term 'inflammation'.

[00141] In some embodiments, said administering is via inhalation.

[00142] In some embodiments, said administering via inhalation comprises administering via an apparatus configured to produce vapor and/or aerosol. In some embodiments, the apparatus is a hand-held device. In some embodiments, the apparatus is selected from nebulizer, inhaler and atomizer. In some embodiments, the apparatus is a respiratory machine. In some embodiments, the apparatus is a mechanical ventilator. In some embodiments, the apparatus is a breathing machine. Each possibility is a separate embodiment of the present invention.

[00143] In some embodiments, the apparatus is a nebulizer. In some embodiments, the apparatus is a MESH ultrasonic nebulizer. In some embodiments, the apparatus is a portable MESH ultrasonic nebulizer.

[00144] In some embodiments, the apparatus is any life support device, such as, a respiratory machine.

[00145] In some embodiment, the apparatus is an oxygen machine, oxygen inhaler, oxygen bag or oxygen cylinder, where inhalation is performed via a face mask connected to the apparatus, wherein the antiviral composition is provided in parallel to oxygen. [00146] In some embodiments, the apparatus is a face mask, linked to a source comprising the antiviral composition, such that, when breathing with the mask, the subject wearing the face mask is also receiving the antiviral composition.

[00147] In some embodiments, the face mask is a medical face mask.

[00148] In some embodiments, the composition is administered via inhalation of the at least one composition, thereby the composition reaches the entire respiratory system, the lungs, the bronchial tubes and/or the nasal cavities.

[00149] The term "pharmaceutically effective amount" is used to refer to an amount that is sufficient to achieve a desired result in a medical treatment. The "pharmaceutically effective amount" can be determined according to the subject's category, age, sex, severity and type of disease, activity of drug, sensitivity to drug, administration time, administration route, excretion rate, and so forth. In some embodiments, the "pharmaceutically effective amount" is the minimum amount required for exerting the desired therapeutic activity. In some embodiments, the "pharmaceutically effective amount" is the amount of therapeutically active antiviral compound(s) to exert a therapeutic effect. The therapeutic effect includes, but is not limited to, treatment of viral induced severe acute respiratory syndrome (SARS), reduction of the risk of infection, reduction of the risk of inflammation, improvement in symptoms associated with viral induced severe acute respiratory syndrome (SARS), cure of inflammation and cure of viral infections by passive or active inhalation treatment of a respiratory. Thus, the term "therapeutically active antiviral compound(s)" as used herein refers to antiviral compound(s) capable of exerting a therapeutic effect.

[00150] In some embodiments, treating infection of the human respiratory system induced by SARSr-CoV in a human subject, comprises protecting the human subject from SARSr-CoV.

[00151] In some embodiments, treating infection of the human respiratory system induced by SARSr-CoV in a human subject, comprises inhibiting the progression of the infection.

[00152] In some embodiments, treating infection of the human respiratory system induced by SARSr-CoV in a human subject, comprises inhibits the activity of a pathogenic agent inducing the disease, suppressing the activity of SARSr-CoV. [00153] In some embodiments, treating infection of the human respiratory system induced by SARSr-CoV in a human subject, comprises preventing the progression of the infection.

[00154] In some embodiments, said treating comprises reliving bronchial congestion.

[00155] In some embodiments, said treating comprises assisting in opening clogged sinus passages.

[00156] In some embodiments, the SARSr is accompanied with at least one respiratory disease or disorder. In some embodiments, the at least one respiratory disease or disorder selected from pneumonia, colds, flu, asthma, bronchiolitis, bronchial congestion, clogged sinus passages and tuberculosis. Each possibility is a separate embodiment of the present invention.

[00157] In some embodiments, the subject in need thereof is a subject diagnosed with infection of the respiratory system induced by SARSr-CoV.

[00158] In some embodiments, the subject in need thereof is a subject having a high probability of being infected by SARSr-CoV.

[00159] In some embodiments, a subject having a high probability of being infected by SARSr-CoV may be a subject susceptible to infection of the respiratory system induced by SARSr-CoV.

[00160] In some embodiments, a subject having a high probability of being infected by SARSr-CoV may be a subject who is at least 40 years old, a heavy smoker, a subject having a family history of respiratory tract diseases, a subject having genetic predisposition to respiratory tract diseases, a subject having cystic fibrosis and combinations thereof. Each possibility is a separate embodiment of the present invention.

[00161] Several genetic risk factors associated with respiratory distress syndrome are known. These include the family of surfactant protein gene allelic variants SP-A, SP-A SP-A2, SP-B, SP-C and SP-D among others. Mutations of SP-B and ABC A3 were shown to be associated with respiratory distress syndrome in a hereditary (family specific) manner. Furthermore, mutations in the genes encoding SP-B (SFTPB), SP-C (SFTPC), and ABCA3 (ABCA3) were shown to disrupt surfactant function and cause respiratory distress in the newborn. A number of transcription factors, including thyroid transcription factor- 1 (TTF-1; also known as NK2 homeobox 1 or thyroid-specific-enhancer-binding protein, CCAAT enhancer binding protein-a(C/EBPa), and forkhead box A2 (Foxa2), have been identified as influencing lung formation and surfactant production as well as homeostasis in late gestation. TTF-1, C/EBRa, and Foxa2 were shown to interact reciprocally to regulate transcriptional targets of surfactant synthesis and peripheral lung maturation. TTF-1, encoded by NKX2-1, is an early marker of lung differentiation and an essential regulator for the expression of SP-A, SP-B, SP-C, and ABC A3. Mutations in NKX2-1 results in respiratory distress syndrome and respiratory failure in newborn infants and in interstitial lung disease in older children. C/EBPa, a member of a family of basic leucine zipper transcription factors, plays an important role in the synthesis and metabolism of surfactant lipids and proteins. Deletion of the CEBPA gene causes the inhibition of lung epithelial cell proliferation and differentiation. Deletion of FOXA2 inhibits branching morphogenesis and epithelial cell differentiation of the lung.

[00162] In some embodiments, a subject having a high probability of being infected by SARSr-CoV is a subject affected with Chronic Obstructive Pulmonary Disease (COPD). COPD is an obstructive lung disease typically characterized by chronic breathing problems and poor airflow. Of the symptoms associated with COPD, the main are shortness of breath and cough with sputum production. COPD is a progressive disease which typically worsens over time.

[00163] In some embodiments, a subject having a high probability of being infected by SARSr-CoV is a subject affected with acute or chronic bronchitis. Chronic bronchitis is an inflammatory disorder characterized by inflammation (swelling) and irritation of the bronchial tubes, causing buildup of mucus.

[00164] In some embodiments, a subject having a high probability of being infected by SARSr-CoV is a subject affected with emphysema. Emphysema is a lung condition that causes shortness of breath. It is characterized by damaged alveoli. In particular, emphysema is gradually formed by the weakening and rapture, over time, of the alveoli resulting with larger air spaces thereby reducing the surface area of the lungs and thus the amount of oxygen that reaches the bloodstream. Most patients who are suffering from emphysema are also diagnosed with chronic bronchitis. Emphysema and chronic bronchitis make up chronic obstructive pulmonary disease (COPD). One of the main causes for COPD is smoking.

[00165] In some embodiments, a subject having a high probability of being infected by SARSr-CoV is a subject affected with lung cancer. Lung cancer is one of the most common and serious types of cancer. Of the two main types of lung cancer, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the former is the most common. NSCLC has several subtypes, including squamous cell carcinoma, adenocarcinoma, large cell carcinoma, adenosquamous carcinoma, sarcomatoid carcinoma, lung carcinoid tumor, adenoid cystic carcinoma and benign lung tumor. Symptoms of lung cancer include persistent cough, chest pain, hoarseness, unexplained loss of appetite and weight, coughing up blood or rust-colored phlegm, shortness of breath, weakness/fatigue, bronchitis, pneumonia or other infections, among others.

[00166] In some embodiments, the SARSr-CoV is COVID-19.

[00167] In some embodiments, the method further comprising co-administering at least one additional agent. In some embodiments, the at least one additional agent comprises one or more essential oils.

[00168] In some embodiments, there is provided a method for reducing the risks of infection of the human respiratory system of at least one human in an enclosed area, including home or public area, wherein the infection is induced by a Severe acute respiratory syndrome-related coronavirus (SARSr-CoV), the method comprising enriching the environment of the enclosed area with the antiviral composition disclosed herein.

[00169] According to some embodiments, the enclosed area is an enclosed private area. According to some embodiments, the enclosed area is a private residential property (e.g. home).

[00170] According to some embodiments, the enclosed area is an enclosed public area

[00171] In some embodiments, reducing the risks of infection by corona virus comprises inhibition or attenuation of cytokine secretion. As exemplified below using the Cytokine Storm Assay, the compositions disclosed herein inhibit, prevent and/or reduce cytokine secretion.

[00172] Inflammatory response is a central component of the immune response against pathogens. White blood cells use a set of sensors to recognize the pathogen and produce cytokines in response. These cytokines trigger inflammation and recruit other cells of the immune system for help. Chemokines such as IL-8 guide the immune cells to the infected tissue and recruit other immune cells. Cytokines, such as interleukin- lb (IL-Ib), IL-6 and TNFa - trigger inflammation, modulate the immune response and act as endogenous pyrogens. [00173] When the production of cytokines is excessive and uncontrolled it is described as “Cytokine storm”. The body struggles to regain control and regulate the response however, when cells fail to terminate the inflammatory response the cytokine storm may have irreversible consequences.

[00174] The roles of the examined cytokines in the cytokine storm is as follows:

Heightened interleukin- lb (IL-Ib) results in fever and organ failure.

High levels of tumor necrosis factor (TNFa) causes massive destruction of the cells lining the blood vessels, which become clotted.

High levels of IL-6 can activate the coagulation pathway and vascular endothelial cells.

Increased levels of IL-6 in the serum of COVID-19-inf ected patients have been correlated with respiratory failure. \

IL-8 is a pro-inflammatory chemokine (a sub-type of cytokines) that plays a role in the progression of the immune response.

IL-10 is most recognized as a regulatory cytokine, recent evidence in COVID-19 patients has linked IL-10 to a potential role in fibrosis, where increased IL-10 expression was reported to induce collagen production and fibrocyte recruitment into the lung.

[00175] It is to be understood that the use of the antiviral composition refers to use of any one or more of the antiviral compositions disclosed herein.

[00176] In some embodiments, enriching the environment of the enclosed public area with the antiviral composition disclosed herein comprises applying a composition comprising the antiviral composition for the purpose of cleaning, dusting, or disinfecting surfaces or regions within the enclosed public area. Accordingly, when the compositions are applied onto said areas and regions, the antiviral composition or the active component(s) thereof, evaporate into the environment of the enclosed public area, thereby enriching said environment with the one or more antiviral compounds of the antiviral composition comprising same. [00177] In some embodiments, the antiviral composition is designed such that it evaporate slowly releasing sufficient amount of the active compounds over a predetermined period of time.

[00178] In some embodiments, the composition comprising the antiviral composition is a disinfectant. In some embodiments, the composition comprising the antiviral composition comprises at least one disinfectant compound. In some embodiments, the at least one disinfectant is non-toxic and safe for inhalation. In some embodiments, the at least one disinfectant compound comprises at least one of propylene glycol and triethylene glycol.

[00179] In some embodiments, the composition comprising the antiviral composition is a detergent. In some embodiments, the composition comprising the antiviral composition comprises at least one detergent. In some embodiments, the at least one detergent is non-toxic and safe for inhalation.

[00180] In some embodiments, the composition comprising the antiviral composition is volatile at room temperature.

[00181] In some embodiments, said enclosed area, such as, public area or a home, is having a ventilation system and/or an air-conditioning system and said enriching the environment of the enclosed area, private or public area, comprises providing, through the ventilation system and/or an air-conditioning system of the area, the antiviral composition.

[00182] The term "providing" as used herein with respect to the at least one antiviral composition, is interchangeable with the terms transmitting, releasing, spreading, dispersing, or any other activity equivalent thereto.

[00183] The term "risk for infection" as used herein refers to the state in which an individual is at increased risk for being invaded by pathogenic organisms.

[00184] In some embodiments, said providing said antiviral composition is performed periodically.

[00185] The term "periodically" as used herein refers to at least two transmissions of the composition, wherein between each two successive transmission of the at least one composition, there is a time period. The time period may be in the order of seconds, or minutes, or hours. The time period may be a fixed, predetermined, time period, and not subject to changes. Alternatively, the time period may change. In some embodiments, the time period between successive transmissions will be set by a processor.

[00186] In some embodiments, the SARSr-CoV is the COVID-19 strain.

[00187] In some embodiments, the enclosed area is a public area. In some embodiments, the public area includes, but is not limited to, commercial facilities, such as, malls, restaurants, bars, stores, storage halls, dark rooms and theatres, healthcare facilities, hospitals, emergency rooms, old age home (nursery homes), hotels, resorts, gymnasiums, rest rooms, vehicles used for public transportation, such as, busses, trains and airplanes, airports, offices and education facilities, such as, schools, libraries and universities.

[00188] It is noted that in the context of the present disclosure, home (e.g. family house and the like), is considered as an enclosed public area.

[00189] Typically, the ventilation system is an electronic system adjusted to control indoor air quality within the enclosed public area. Controlled indoor quality may be achieved by diluting and displacing indoor pollutants and by providing thermal comfort. Thermal comfort may be hitting/cooling and/or humidifying or dehumidifying the indoor air.

[00190] In some embodiments, the ventilation system comprises a processor functionally connected to the ventilation system, wherein the processor is configured to operate the transmission of the antiviral composition at predetermined time periods.

[00191] In some embodiments, the processor is further configured to determine the length of time between successive transmissions, namely, the length of inactive time period during which the ventilation system does not actively provides/transmits/spreads the composition. In some embodiments, determination of the length of each inactive time period is based on the number of humans within the enclosed public area.

[00192] In some embodiments, the processor is configured to carry out the following: determining, or setting, the time period between two successive transmissions of the antiviral composition, through the ventilation system, into the environment of the enclosed public area; monitoring, in real time, the number of humans within the enclosed public area; and/or determining the pharmaceutically effective amount to be released from the ventilation system at each period based on the number of people in the enclosed public area or the density (i.e. number of people per square meter).

[00193] In some embodiments, the processor is a computer processor linked to a computer software wherein the computer software directs the computer processor to collect data on the number of humans residing in the enclosed public area based on which determine the pharmaceutically effective amount of the antiviral composition.

[00194] In some embodiments, the computer comprises any one of computing system, server and computing device.

[00195] In some embodiments, the computer software comprises processor-executable instructions that are stored on a non-transitory computer readable medium. The computer software may also include stored data. The processor may be functionally linked to a computer readable medium storing data, such as, pharmaceutically effective amount per number of people, per given size of an enclosed area. The tangible computer readable medium may be a magnetic storage, optical storage, random access memory (RAM), read only memory (ROM), or any other tangible medium.

[00196] It is understood that the computer-related methods, steps, processes described herein are implemented using software stored on non-volatile or non-transitory computer readable instructions that when executed configure or direct a computer processor or computer to perform the instructions.

[00197] Each of the system, server, computing device, and computer described in this application can be implemented on one or more computer systems and be configured to communicate over a network. They all may also be implemented on one single computer system. In one embodiment, the computer system includes a bus or other communication mechanism for communicating information, and a hardware processor coupled with bus for processing information.

[00198] The computer system also includes a main memory, coupled to bus for storing information and instructions to be executed by processor. Main memory also may be used for storing temporary variables or other intermediate information during execution of instructions to be executed by processor. Such instructions, when stored in non-transitory storage media accessible to processor, render computer system into a special-purpose machine that is customized to perform the operations specified in the instructions.

[00199] In some embodiments, the method herein is performed by the computer system in response to the processor executing one or more sequences of one or more instructions contained in main memory. Such instructions may be read into main memory from another storage medium, such as storage device. Execution of the sequences of instructions contained in main memory causes the processor to perform the process steps described herein. In alternative embodiments, hard-wired circuitry may be used in place of or in combination with software instructions.

[00200] The term storage media as used herein refers to any non-transitory media that store data and/or instructions that cause a machine to operation in a specific fashion.

[00201] In some embodiments, the SARSr-CoV is accompanied with at least one respiratory disease or disorder. In some embodiments, the at least one respiratory disease or disorder is selected from pneumonia, colds, flu, asthma, bronchiolitis, bronchial congestion, clogged sinus passages, tuberculosis, sinusitis and pharyngitis. Each possibility is a separate embodiment of the present invention.

[00202] In some embodiments, reducing the risks of infection of the human respiratory system comprises inhibiting infection of the human respiratory system.

[00203] In some embodiments, reducing the risks of infection of the human respiratory system comprises preventing the formation of infection of the human respiratory system.

[00204] In some embodiments, reducing the risks of infection of the human respiratory system comprises alleviating the body's immune response.

[00205] In some embodiments, the method further comprising prior to said providing, obtaining, from the processor, periodical updates on the number of humans within the enclosed public area, and accordingly adjusting the rate of release, or the dose, of the at least one antiviral composition provided each period, such that the effective amount provided to the environment of the public area each time is pharmaceutically effective.

[00206] In some embodiments, the enclosed public area has an entrance, wherein the processor is functionally linked to a sensor, the sensor is located at the entrance, and wherein the sensor is configured to transmit notifications to the processor indicating the entrance or exit of a human subject.

[00207] In some embodiments, the enclosed public area has a plurality of entrances, wherein the processor is functionally linked to a sensor, the sensor is located at each entrance of the enclosed public area, wherein the sensor is configured to transmit notifications to the processor indicating the entrance or exit of a human subject.

[00208] In some embodiments, the processor is configured to collect and store clinical data from the human subject(s) at the enclosed public area. In some embodiments, the clinical data include, but is not limited to, body temperature, presence/absence of coughing, presence/absence of sweat, frequency of motion.

[00209] In some embodiments, the sensor is configured to collect and store clinical data from the human subject(s) at the enclosed public area. In some embodiments, the clinical data include, but is not limited to, body temperature, presence/absence of coughing, presence/absence of sweat, frequency of motion.

[00210] In some embodiments, the sensor is configured to collect the clinical data, transfer it to the processor, wherein the processor is configured to store that date or transfer the date to storage. The stored data can be used for learning on disease progression, developing prevention strategies, monitoring the effect of the preventive strategy and any other purpose useful for monitoring, treating and preventing the viral disease, infection and/or inflammation induced thereby.

[00211] In some embodiments, said enclosed public area is having at least one diffuser and said enriching the environment of the enclosed public area comprises providing, through the at least one diffuser, the antiviral composition.

[00212] In some embodiments, the at least one diffuser is configured to release the antiviral composition.

[00213] The term "diffuser" as used herein refers to a device that provides mist/aeroso/fumes. The diffuser may be based on commercial devices, such as, an oil (aroma) diffuser, a humidifier, an electronic diffuser and an ultrasonic diffuser. The diffuser may disperse the antiviral composition mechanically, or electronically. The dispersion may be controlled manually, or electronically. The electronic control can be though physical connection to a processor or though wireless communication. The wireless communication may be based on radio broadcast (RF), Infrared (IR), satellite, microwave and Bluetooth, or any other wireless communication suitable to enable communication between the processor, or components associated therewith, and the diffuser.

[00214] In some embodiments, said release of said antiviral composition is performed periodically.

[00215] In some embodiments, the diffuser is configured to release said antiviral composition, automatically, at predetermined time periods.

[00216] In some embodiments, the diffuser is configured to release said antiviral composition, manually.

[00217] In some embodiments, the diffuser comprises, or functionally connected to, a processor, wherein the processor is configured to operate the release of the antiviral composition at predetermined time periods.

[00218] In some embodiments, the processor is further configured to determine the length of time between successive transmissions, namely, the length of inactive time period during which the diffuser does not actively release the antiviral composition. In some embodiments, determination of the length of each inactive time period is based on the number of humans within the enclosed public area.

[00219] In some embodiments, the processor is configured to carry out the following: determining, or setting, the time period between two successive transmissions of the antiviral composition, through the diffuser, into the environment of the enclosed public area; monitoring, in real time, the number of humans within the enclosed public area; and/or determining the pharmaceutically effective amount to be released from the diffuser at each period based on the number of people in the enclosed public area or the density (i.e. number of people per square meter).

[00220] In some embodiments, the processor is a computer processor linked to a computer software wherein the computer software directs the computer processor to collect data on the number of humans residing in the enclosed public area based on which determine the pharmaceutically effective amount of the antiviral composition.

[00221] Without being bound by any theory, it is presumed that use of a diffuser for enriching the environment of an enclosed public area is appropriate to relatively small enclosed public areas.

[00222] Examples

[00223] Example 1: Cytotoxicity evaluation in human lung fibroblasts cells.

[00224] Human lung fibroblasts MRC-5 cells were plated on two 96 well plates, in their culture medium (EMEM, at lxl0 ⁴ eells/well). Once attached (following about 1 day incubation), the culture medium was discarded, and 100 pL of assay media (EMEM with 1% FBS, 2mM L-Glutamine and 1% Penicillin-Streptomycin) supplemented with the following test compounds was added to the cells: CBD at 2, 5 and 10 pg/ml; NT-VRL1 (Table 1, below) at 5, 10, 50 and 100 pg/ml; and combinations of CBD (1, 3 and 5 pg/ml) with NT-VRL1 (10 pg/ml). Control wells were either supplemented with medium devoid of the test compounds (untreated cells) or were supplemented with pyrazofurin (2, 5 and 10 pg/ml) or with Glycyrrhizin alone (100, 500 and 1,000 pg/ml), as positive control.

[00225] Following incubation (about 72h), cell viability was assessed (XTT assay) for determining non-toxic concentrations and is presented in percentages relative to viability of untreated cells (Fig. 1, line stretched along 100% cell viability, corresponding to cell viability of non-treated cells). Non-cytotoxic concentrations were assigned to concentrations that did not lead to excess cell death as compared to untreated cells. As seen in Figure 1, the non-toxic concentrations were: 0.1 pg/mL < NT-VRL-1 < 20 pg/mL, for CBD + NT-VRL-1, 0.1 pg/mL < CBD < 2.5 pg/mL, 0.1 pg/mL < Pyrazofurin < 10 pg/mL, and 10 pg/mL < Glycyrrhizin < 500 pg/mL.

[00226] Table 1. Antiviral compositions comprising at least three terpenes and/or terpenoids

NT-VRL 1 NT-VRL 2 NT-VRL 3 NT-VRL 4

Terpene/Terpenoid % Terpene/Terpenoid % Terpene/Terpenoid % Terpene/Terpenoid ¹ % b-Pinene 1.5 a-Terpineol 7.03 a-Humulene 0.5 1,8 Cineol

(eucalyptol)

¹ NT-VRL-4 is a water-based formulation including about 2% API - terpene/terpenoids composition) p-cymene 1.5 b-Pinene 5.29 a-Phellandrene 0.5 a-Caryophyllene

(a-humulene)

D-Limonene 1.5 Borneol 5.29 a -Pinene 0.5 a-Phellandrene b-Myrcene 1.5 Myrcene 2.46 a -Terpinene 3 a-Pinene

Caryophyllene 6 Caryophyllene 0.44 a Terpineol 5

Oxide Oxide a-Terpinene

Eucalyptol 10 1,8 Cineol 0.1 b -Caryophyllene 5 a-Terpineoi

Glycyrrhizic acid 1.5 Menthol 5.29 b -Myrcene 0.5 b-Caryophyllene

Carvacrol 6 Carvacrol 0.66 b-Pinene 5 b-Pinene

Cadinene 1.5 Glycyrrhizin 13.21 Cadinene 0.5 Bomeol a-Pinene 10 a-Pinene 0.18 Carvacrol 5 Cadinene

Citral 10 Citral 0.12 Caryophyllene 5

Oxide Camphor

L-Carvone 1.5 a-Terpinene 5.29 Citral 0.5 Carvone

Linalool 1.5 Trans- b-Ocimene 5.29 D-Camphor 0.5 Caryophyllene

Oxide a-Phellandrene 6 a-Phellandrene 1.8 D-Limonene 3 Citral (lemonal)

Gamma-Terpinene 6 g-Terpinene 0.9 Eucalyptol 3 g-Terpinene Santalol 6 Santalol 1.31 g-Terpinene 3 Glycyrrhizin b -Caryophyllene 10 b-Caryophyllene 0.07 Glycyrrhizic acid 50 Limonene a-Humulene 1.5 Limonene 5.64 L-bomeol 0.5 Menthol

Sabinene 1.5 Cadinene 5.29 L-Carvone 0.5 Myrcene a-Terpinene 1.5 Sabinene 5.29 Linalool 0.5 P-cymene

L-menthol 1.5 Linalool 7.93 L-menthol 0.5 Sabinene

D-Camphor 1.5 Camphor 1.98 p-cymene 3 Santalol

L-bomeol 1.5 Carvone 5.48 Sabinene 0.5 Thymol a-Terpineol 1.5 a-Caryophyllene 5.29 Santalol 0.5 Trans- b-Ocimene

Thymol 6 Thymol 1.32 Thymol 3 b-Ocimene 1.5 P-cymene 7.08 b-Ocimene 0.5

[00227] Example 2: Anti-viral effect of the terpen/terpenoid compositions in human lung fibroblasts cells

[00228] An antiviral composition comprising at least three terpenes and/or at least three terpenoids (termed NT-VRL-1 and NT-VRL-3; Table 1) was tested in vitro for its activity against 229E human Coronavirus strain (HCoV-229E), with and without the addition of cannabidiol (CBD), using human lung fibroblasts (MRC-5 cells). [00229] MRC-5 cells were plated at lxlO ⁴ cells/well in 96 well plates, in culture medium (EMEM) supplemented with 10% fetal calf serum, and incubated at 37°C, 5% CO2. The next day, cells were divided into three groups of treatments: (1) Cells Pretreatment; (2) Virus Pretreatment; and (3) Post adsorption.

[00230] (1) Cells pretreatment (cells exposed to test compounds prior to exposure to virus)

- medium was discarded, and 100 pL of EMEM supplemented with 1% fetal calf serum was added to the cells, supplemented with the test compounds. The cells were incubated with the test compounds for about 1 hour (incubation - at 34°C, 5% CO2). Next, 1 pL of medium or virus (HCoV-229E) at 100 times the concentration of the infective dose were added to the cells. The cells were incubated for additional 72+2 hours. A representative photo of the cells in each treatment 24, 48 and 72 hours post infection was taken using an inverted microscope (Figs. 2A

- 2N, taken 72 hours post infection post infection). The preventive effect of the tested compounds was assessed by evaluating cell viability using XTT assay where the results are presented in percentages relative to viability of untreated cells (Fig. 3, line stretched along about 40% cell viability, corresponding to cell viability of untreated cells which were exposed to the corona virus).

[00231] As seen in Figure 3, the viability of untreated cells was reduced to -40% after being incubated with HCoV-229E alone. Pre-incubation of the cells prior to virus addition with all the compounds rescued the cells and elevated cells’ viability over 40% (Fig. 3). Stated otherwise, as shown in Fig. 3 all tested compounds prevented, in a significant manner, the toxic effect exerted by the virus. Of note, the combination of 10 pg/mF NT-VRF-1 with 1 pg/mF CBD was the most efficient treatment providing the highest percentage of cell viability. In fact, the combination of NT-VRF-1 with CBD maintained cell viability at 100%. The preventive pattern exerted by NT-VRF-1 and NT-VRF-3 was also observed in the cytopathic effect seen under the microscope after 72 hours. Swelling and clumping of the MRC-5 cells was observed 72 hours post viral infection. However, cell pretreatment with NT-VRF-1 alone (e.g. Fig 2E) and with the addition of CBD (e.g. Fig 2F) before viral infection prevented the cytopathic effect of the virus.

[00232] (2) Virus pretreatment (HCoV-229E was incubated with the compounds before being introduced to the MRC-5 cells.) - 120 pF of EMEM supplemented with 1% fetal calf serum was added to the wells, supplemented with the test compounds at nontoxic concentrations, and 1.2 pF medium (control) or virus (HCoV-229E ) at 100 times the concentration of the infective dose was added to the wells. The virus + test compounds mix in U shape plate was incubated for 1 hour at 34°C, 5% CO2. Next, 100 pL of the virus + compounds mix was added to the cells after medium was removed and the cells were incubated for an additional 72+2 hours at 34°C, 5% CO2. A representative photo using an inverted microscope was taken of the cells in each treatment 24, 48 and 72 hours post infection (e.g. Figs. 4A - 4N, discussed below, taken 72 hours post infection). The virus-induced cytopathic effect was observed in comparison with the parallel virus control and cell control. Finally, cells were subjected to XTT assay.

[00233] As seen in Figure 5, the viability of untreated cells incubated with Corona virus (FlCoV-229E strain) alone was reduced to -80%. Accordingly, the antiviral effect of the tested compounds was assessed by evaluating cell viability using XTT assay where the results are presented in percentages relative to viability of untreated cells (Fig. 5, line stretched along about 80% cell viability, corresponding to cell viability of untreated cells which were exposed to the corona virus). Pre-incubation of the virus with a combination of 10 pg/mL NT-VRL-1 and 1 pg/mL CBD prior to its introduction to host cells elevated cells’ viability over 80% in a significant manner (p < 0.001, T-test). In addition, virus pretreatment with NT-VRL-1 and with CBD prevented cytopathic effect post virus introduction (Figure 5). Without being bound by any theory or mechanism of action, the protective effect exerted by NT-VRL-1 against coronavirus infection, is specific, since NT-VRL-1 by itself had no effect on the proliferation of non-infected cells.

[00234] The viral replication and cytopathic effect in MRC-5 cells of pretreatment the virus FlCoV-229E with the terpenes/terpenoids compositions, alone or together with CBD, was also visible. Figure 4A presents healthy, non-infected, MRC-5 cells. Figures 4B, 4C and 4F present MRC-5 cells 72 hr post infection with FlCoV-229E (pretreated with assay medium), 72 hr post infection with FlCoV-229E that was pretreated with terpenes, and 72 hr post infection with FlCoV-229E that was pretreated with terpenes and CBD, respectively.

[00235] (3) Post adsorption (cells were exposed to the virus, then treated with the test compounds) - EMEM supplemented with 1% fetal calf serum was added to the wells, with or without 1 pL of corona virus at 100 times the concentration of the infective dose. The cells were incubated for about 1 hour at 34°C, 5% CO2. Then, medium was discarded, and 100 pL of EMEM supplemented with 1% fetal calf serum was added to the cells, supplemented with the test compounds according to each nontoxic concentration and 1 pL of media or virus at 100 times the concentration of the infective dose. The cells were incubated for additional 72+2 hours. A representative photo using an inverted microscope was taken of the cells in each treatment 24, 48 and 72 hours post infection (e.g. Figs. 6A - 6N, discussed below, taken 72 hours post infection). The virus-induced cytopathic effect was observed in comparison with the parallel virus control and cell control. Finally, cells were subjected to XTT assay.

[00236] The viability of untreated cells incubated with Corona virus (FlCoV-229E strain) alone was reduced to -70%. Accordingly, the antiviral effect of the tested compounds was assessed by evaluating cell viability using XTT assay where the results are presented in percentages relative to viability of untreated cells (Fig. 7, line stretched along about 70% cell viability, corresponding to cell viability of untreated cells which were exposed to the corona virus).

[00237] Under these conditions, the following treatments inhibited or attenuated the cytotoxic effect of corona virus (namely, elevated cell viability over 70%) in a significant manner: NT-VRL-1 (10 pg/mL) with or without 1 pg/mL CBD; Glycyrrhizin; Pyrazofurin; and CBD. Without being bound by any theory or mechanism of action, the protective effect exerted by NT-VRL-1 against coronavirus infection, is specific, since NT-VRL-1 by itself had no effect on the proliferation of non-infected cells. The effect of terpenes/terpenoids compositions post infection on the replication and cytopathic effect of FlCoV-229E in MRC-5 cells could also be observed under inverted microscope (Figures 6 A to 6N): healthy MRC-5 cells (Fig. 6A) are shown next to MRC-5 cells exposed to the virus (Fig. 6B) and MRC-5 cells exposed to the virus, 72 hours after being treated with (Fig. 6C) NT-VRL-1 and with NT-VRL- 1 + CBD (6D).

[00238] Fxample 3: A preclinical in vitro immunological evaluation of the cytotoxicity of the terpen/terpenoid compositions in peripheral blood mononuclear cells (PBMCs)

[00239] The cytotoxicity of the terpen/terpenoid compositions according to the present disclosure (also termed 'test compounds') was tested in vitro in human PBMCs was evaluated.

[00240] Commercial frozen PBMCs were used and the test compounds were diluted in sterile saline (termed Fl/NT-VRL-1 or F2/NT-VRL-2; Table 1) or in DMSO (termed Fl-D or F2-D) to a final concentration of 40 mg/ml (4% v/v). [00241] The primary human PBMCs were thawed and suspended in culture media where cell viability was assayed using Alamar blue® reagent. The control compounds included saline and DMSO alone as non-toxic solutions and Triton (1%) as a cytotoxic reagent.

[00242] AlamarBlue®-Cell Viability reagent is a non-toxic, cell-permeable compound that detects metabolically active cells and was used for the quantitative analysis of cell viability/cytotoxicity. The aim of this assay was to choose the highest concentrations which are non-toxic to the cells, in order to verify that an inhibition effect on cytokine secretion levels (measured in Example 4, below) is due to an anti-inflammatory effect rather than a cytotoxic effect. The results of the cytotoxicity test are summarized in the Fig. 8. In the positive control wells, cells were treated with Triton 1 % (a popular non-ionic surfactants used for permeabilizing cells were used to demonstrate full cytotoxicity (or no viability). The results preseted in Fig. 8 show that triton caused significant reduction in cell viability. All other control samples (CBD, Dex, NaCl 0.9%, DMSO, LPS and LPS+Dex) showed no reduction in the levels of AlamarBlue® i.e. no toxic effect that reduced cell viability of PBMCs. The percentage of viable cells in all treatment groups below 60pg/ml, was similar to controls. Accordingly, the working concentrations of the test compounds was set to <20pg/ml for samples diluted in DMSO and <40pg/ml for samples diluted in saline.

[00243] Example 4: A preclinical in vitro immunological evaluation of the terpen/terpenoid compositions in peripheral blood mononuclear cells (PBMCs)

[00244] The terpen/terpenoid compositions were tested in in vitro assays measuring the effect on innate immune response in primary human PBMCs were used for the cytotoxicity and cytokine secretion assays. Fluman PBMCs were thawed and suspended in a designated culture media and the controls and test compounds were diluted in culture media to achieve the final assay concentration. Cells were incubated with the test compounds and controls for 1 hour, treated with lOOng/ml LPS and incubated for 24 hours. Dexamethasone (DEX; 1 mg/ml) served as positive control. Following incubation, the supernatants were collected, the levels of a panel of secreted cytokines were measured by ELISA and the optical density were determined by ‘CLARIOStar-plus’ plate-reader. The concentration of cytokines (pg/ml) were calculated using a standard curve.

[00245] In a first experiment the tested compositions were assayed for their effect on LPS- induced pro-inflammatory cytokine secretion by human PBMCs. PBMCs were cultured in triplicates. Cells were incubated with the indicated concentration of NT-VRL-1 in saline (also termed "FI"), NT-VRL-2 in saline (also termed "F2"), NT-VRL-1 in DMSO (also termed "Fl- D") and NT-VRL-2 in DMSO (also termed "F2-D") for about an hour, followed by treatment with 100 ng/ml LPS and further incubated for 24 hours. Dexamethasone (DEX, 1 pg/ml) served as positive control. At the end of the incubation, the supernatants were collected and the levels of a panel of secreted cytokines were measured by ELISA.

[00246] Results for all four cytokines (IL-Ib, TNF-a, IL-6 and IL-8) are presented in Figs. 9A - 9D, respectively. The results show that both compositions had a dose-depended inhibitory effect on LPS-induced cytokine secretion by PBMCs. The results further suggest that FI is relatively more potent than F2 as an anti-inflammatory agent. In addition, the inhibitory effect of the test composition was higher than that of CBD alone, with respect to most cytokines. Furthermore, the combination of the test composition with CBD showed a strong inhibitory effect suggesting a synergy between CBD and the terpen/terpenoid compositions.

[00247] In addition, the formulation, diluted both in saline and DMSO had a dose-depended effect on LPS-induced cytokine secretion. However, compared to saline, formulations diluted in DMSO showed a more prominent inhibition of LPS-induced cytokine secretion. Addition of CBD (2 pg/ml) together with the compositions in DMSO exerted the highest inhibition of cytokine secretion.

[00248] In a second experiment a second donor of PBMCs was added, as a biological replicate. The results of the second experiment, performed on PBMCs from a different donor show a differential effect of the various treatments, as shown in Figs. 10A - 10D.

[00249] The test compounds demonstrated a dose-depended inhibition of LPS-induced IL- 1b and IL-6 secretion, as shown in Figs. 10A and IOC, respectively. As in the first experiment, FI was more potent than F2 as an anti-inflammatory agent. However, only a mild effect on LPS-induced TNF-a and IL-8 secretion was detected (Figs. 10B and 10D, respectively).

[00250] In summary, high levels of pro-inflammatory cytokines are in direct correlation with the disease severity, that indicated on the immune response. By reducing the cytokine storm that occurs in many inflammatory conditions, the immune system regains control of the infection. Culturing human-PBMCs as exemplified herein, is a unique cell-based model. The cells were obtained from healthy donors making this model a beneficial ex-vivo model. One great advantage using this model, is that the response induced in culture highly correlates to human immune response. As such, results also reflect the known clinical variation among humans. In the above experiments two different donors were tested (one in each experiment, N=2). The differential cytokine secretion profile in these two experiments indicate the donor variation. To conclude, the results establish that the terpenes/terpenoids compositions disclosed herein exert anti-inflammatory activity .

[00251] Example 5: Phase II, double-blind, placebo-controlled clinical study designed to evaluate the effect of the terpene/terpenoid compositions in patients diagnosed with COVID- 19

[00252] A composition comprising NT-VRL-4 (Table 1) is given via inhalation, 1 to 5 times a day, to patients diagnosed with COVID-19. During the screening visit, patients are randomized to the following, in 1:1 ratio: Arm 1 - Patients treated with NT-VRL-4, given as an add-on therapy to standard treatment, 1 to 4 times a day, for about two weeks; Arm 2 - Patients given with Placebo, 1 to 4 times a day, for about two weeks, in addition to standard treatment. During the study time, patients are monitored for adverse events. Additional time is required for follow up (until hospital discharge) in order to check side effects and study drug efficacy.

[00253] The primary endpoints are: Time to clinical improvement, defined as a National Early Warning Score 2 (NEWS2) of </= 2 Maintained for 24 Hours in comparison to routine treatment; and Percentage of participants with definite or probable drug related adverse events. The Secondary Endpoints are: Time until negative PCR; Proportion of participants with normalization of fever and oxygen saturation through day 14 since onset of symptoms; COVID-19 related survival; Incidence and duration of mechanical ventilation; Incidence of Intensive Care Init (ICU) stay; Duration of ICU stay; and Duration of time on supplemental oxygen.

[00254] Inclusion Criteria: Hospitalized COVID-19 patient in stable moderate condition (i.e., not requiring ICU admission); Men and Women aged 18-75; and must be under observation or admitted to a controlled facility or hospital (home quarantine is not sufficient).

[00255] Exclusion Criteria: Tube feeding or parenteral nutrition; Patients who are symptomatic and require oxygen (Ordinal Scale for Clinical Improvement score >3) at the time of screening; Respiratory decompensation requiring mechanical ventilation; uncontrolled diabetes type 2; Autoimmune disease; Pregnant or lactating women and Admission to ICU > 24 hours. [00256] Any condition which, in the opinion of the Principal Investigator, would prevent full participation in this trial or would interfere with the evaluation of the trial endpoints.

[00257] Day 1 - Screening. Prior to engaging in any study procedures, the subject must meet the inclusion/exclusion criteria by history (which includes a signed declination), and review and sign an ICF. The following procedures are performed during the visit: Inclusion/Exclusion criteria evaluation; ICF (Informed Consent Form); Medical history; Concomitant medication; Physical examination; Vital signs; Flematology blood test; Biochemistry blood test; COVID- 19 PCR test; E.C.G; Randomization in 1:1 ratio (NT-VRL-4 + standard of treatment / Placebo + standard of treatment) and study drug administration.

[00258] Days 2-14. The following procedures are performed: Concomitant medication; Adverse Events assessment; Physical examination; Vital signs; Flematology blood test; Biochemistry blood test; COVID-19 PCR test; E.C.G; and Study drug administration.

[00259] Follow up - Flospital Discharge. The following procedures are performed: Concomitant medication; Adverse Events assessment; Physical examination; Vital signs; Flematology blood test; and Biochemistry blood test.

[00260] After completion of the study, statistical analysis is performed and the therapeutic effect of NT-VRL-4 in preventing, attenuating, curing corona virus and infections associated therewith is evaluated.

[00261] One skilled in the art readily appreciates that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned, as well as those inherent therein.

[00262] While this invention has been disclosed with reference to specific embodiments, it is apparent that other embodiments and variations of this invention may be devised by others skilled in the art without departing from the true spirit and scope of the invention. The appended claims are intended to be construed to include all such embodiments and equivalent variations.