Food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, and miscellaneous goods for preventing or treating coronavirus disease 2019 (COVID-19)

Abstract

To provide a food composition, a pharmaceutical composition, a quasi drug composition, a cosmetic composition and sundries for preventing or treating COVID-19.SOLUTION: The present invention discloses a food composition, a pharmaceutical composition, a quasi drug composition, a cosmetic composition and sundries for preventing or treating COVID-19, each comprising at least one selected from a cat's claw extract, a ginger extract, pteropodine and a pharmaceutically acceptable salt thereof, isopteropodine and a pharmaceutically acceptable salt thereof, 6-gingerol and a pharmaceutically acceptable ether thereof and 6-shogaol and a pharmaceutically acceptable ether thereof.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a food composition, a pharmaceutical composition, a quasi-drug composition, a cosmetic composition, and a miscellaneous goods for preventing or treating coronavirus disease 2019 (COVID-19).

Background Art

[0002] In December 2019, the first case of coronavirus disease 2019 (COVID-19) was confirmed in Wuhan City, Hubei Province, China, and the infection has spread all over the world. The causative novel coronavirus (SARS-CoV-2) is a type of coronavirus, a positive-strand RNA virus belonging to the Coronavirinae subfamily of the Coronaviridae family. Coronaviruses are the cause of common colds, and also include the viruses of severe acute respiratory syndrome (SARS) that spread mainly in Asia in 2003 and Middle East respiratory syndrome (MERS) that has been spreading in the Middle East since 2012. The main symptoms of COVID-19 are fever, general malaise, and respiratory symptoms. Approximately 80% of patients recover with mild symptoms, but approximately 20% experience worsening of pneumonia symptoms, and approximately 5% become severe cases that require intensive care such as mechanical ventilation. There are also reports of cases where the condition deteriorates rapidly. As a factor contributing to the aggravation, it is considered that an excessive immune reaction occurs due to a cytokine storm, which is an excessive release of cytokines from immune cells, and organs such as the lungs are damaged.

[0003] As of the filing date of this application, there is no specific therapeutic agent for coronavirus disease 2019 (COVID-19), and existing drugs are only being repurposed. The antiviral drug remdesivir has been confirmed to have the effect of shortening the treatment period for severely ill COVID-19 patients and has received special approval in Japan. However, in principle, the drug is only administered to severely ill patients, and there are concerns about its safety, such as a high frequency of renal and hepatic dysfunction. Furthermore, there is also the issue of limited supply of remdesivir. In addition, there is a report that dexamethasone, a steroid drug, has also reduced deaths in severe cases, and it has become the second drug approved in Japan for the treatment of COVID-19. However, the US National Institutes of Health (NIH) treatment guidelines recommend its use only for severely ill patients, and the treatment method for mild cases has not been established. Other therapeutic agents are off-label uses, and their efficacy and safety are unclear as they are still being verified. Regarding vaccination, which is generally an effective means of preventing viral infections, although there are some vaccines for which clinical trials have been initiated, none have been put into practical use. Given these circumstances, the development of preventive and therapeutic agents that are effective against COVID-19, have high safety, and can be stably supplied is an urgent issue.

[0004] On the other hand, there are reports using molecular docking methods on the interaction between natural-derived components and the proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), indicating that epigallocatechin gallate, anthocyanidin, curcumin, etc. may have antiviral effects (Non-Patent Documents 1 and 2).

Prior Art Documents

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0006] However, these are the results of computer simulations and have not been demonstrated at the cellular or animal levels. As described above, there are still concerns about the safety of the currently used therapeutic drugs, and the supply is limited. Therefore, there is a demand for the provision of food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, and sundries for prevention or treatment that utilize natural products with high safety and easy availability of raw materials to solve such problems.

[0007] An object of the present invention is to solve the above-described conventional problems and achieve the following objects. That is, the present invention aims to provide a food composition, a pharmaceutical composition, a quasi-drug composition, a cosmetic composition, and sundries for preventing or treating coronavirus infectious diseases, which contain natural products with high safety and easy availability of raw materials as components.

Means for Solving the Problems

[0008] To solve the above problems, the inventors of the present invention have conducted intensive studies on a highly safe natural product that can be widely used in foods, pharmaceuticals, quasi-drugs, cosmetics, and sundries as a preventive or therapeutic agent for coronavirus infectious diseases, and as a result, the present invention has been achieved.

[0009] That is, the present invention is a food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, or miscellaneous goods having a preventive or therapeutic effect against novel coronavirus, preferably containing as an active ingredient at least any one of cat's claw extract, ginger extract, pteropodine and its pharmaceutically acceptable salts, isopteropodine and its pharmaceutically acceptable salts, 6-gingerol and its pharmaceutically acceptable ethers, and 6-shogaol and its pharmaceutically acceptable ethers. So far, the effects of cat's claw extract, ginger extract, pteropodine, isopteropodine, 6-gingerol, and 6-shogaol against novel coronavirus are completely unknown, and this is a new finding by the intensive research of the present inventors.

[0010] More specifically, the present invention is as follows. That is, the preventive or therapeutic agent for novel coronavirus infection according to one aspect of the present invention contains an extract of Uncaria tomentosa, and preferably contains this as an active ingredient. Here, the "agent" in the preventive agent and therapeutic agent is a term used as a classifier, and the term "agent" is used to mean something having a pharmacological function, but this does not necessarily mean a pharmaceutical composition (drug). This preventive agent and therapeutic agent can be used in a food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, or miscellaneous goods as its active ingredient.

[0011] In addition, the preventive or therapeutic agent for novel coronavirus infection according to another aspect of the present invention contains an extract of Zingiber officinale, and preferably contains this as an active ingredient.

[0012] In addition, the preventive or therapeutic agent for novel coronavirus infection according to another aspect of the present invention contains at least any one of pteropodine and its pharmaceutically acceptable salts, and preferably contains this as an active ingredient.

[0013] In addition, the preventive or therapeutic agent for coronavirus disease according to another aspect of the present invention contains at least one of Isopteropodine and a pharmaceutically acceptable salt, and preferably contains this as an active ingredient.

[0014] In addition, the preventive or therapeutic agent for coronavirus disease according to another aspect of the present invention contains at least one of 6-Gingerol and a pharmaceutically acceptable ether, and preferably contains this as an active ingredient.

[0015] In addition, the pharmaceutical composition for preventing or treating coronavirus disease according to another aspect of the present invention contains at least one of 6-Shogaol and a pharmaceutically acceptable ether, and preferably contains this as an active ingredient.

Advantages of the Invention

[0016] As described above, according to the present invention, it is possible to provide a food composition, a pharmaceutical composition, a quasi-drug composition, a cosmetic composition, and miscellaneous goods for preventing or treating coronavirus disease, which contain natural products with high safety and easy availability of raw materials as components. The present invention is a natural-derived extract or compound, and because it is excellent in safety, it is suitable for being formulated or added to foods, pharmaceuticals, quasi-drugs, cosmetics, and miscellaneous goods for use.

Brief Description of the Drawings

[0017] A brief description of the figures in the examples is as follows.

Figure 1

Figure 2

Figure 3

Figure 4

Best Mode for Carrying Out the Invention

[0018] Hereinafter, embodiments of the present invention will be described in detail. The present invention can be implemented in many different forms and is not limited only to the specific examples shown in the following embodiments and examples.

[0019] The prophylactic or therapeutic agent for coronavirus disease of the present invention contains at least any one of cat's claw extract, ginger extract, pteropodine and its pharmaceutically acceptable salts, isopteropodine and its pharmaceutically acceptable salts, 6-gingerol and its pharmaceutically acceptable ethers, and 6-shogaol and its pharmaceutically acceptable ethers. Preferably, it contains at least any one of these as an active ingredient, and further contains other components as necessary.

[0020] The cat's claw extract and ginger extract can be easily obtained by methods generally used for plant extraction. Each plant extract includes an extract of the extraction raw material, a dried product obtained by drying a diluted solution of the extract, or any of their crude purified products or purified products. Also, the used part of the extraction raw material is not limited as long as the above effects can be obtained, but it is preferable to use the bark for the cat's claw extract and the rhizome for the ginger extract.

[0021] Furthermore, the method for extracting the above plant extract is not particularly limited and can be carried out according to methods well-known to those skilled in the art. As the extraction solvent, water, alcohol-based solvents, and organic solvents such as acetone, esters, polyhydric alcohols, and ethers can be used. These solvents may be used alone or in combination. Among these, it is preferable to use ethanol, and it is more preferable to use hydrous ethanol with an ethanol content of 10% - 95% (v / v). The amount of the extraction solvent, the extraction temperature, the extraction time, and the extraction method are not limited as long as the composition capable of exhibiting the above effects can be obtained. The amount of the extraction solvent is preferably 1 - 100 parts by weight based on the dry weight of the raw material. The extraction temperature is preferably 4 - 90°C. The extraction time is preferably 30 minutes to 1 week. The extraction method can be carried out by any method such as stirring extraction, immersion extraction, countercurrent extraction, ultrasonic extraction, supercritical extraction, etc.

[0022] Also, the above extract may be the filtrate itself obtained by filtering the obtained extract solution, a concentrated solution obtained by concentrating the filtrate, a dried product obtained by drying the concentrated solution, or a crude product or purified product thereof. The concentration method and the drying method can be carried out by any method. If necessary, excipients such as dextrin may be added. When purification is carried out, it can be carried out according to means known to those skilled in the art such as synthetic adsorption resins, activated carbon, ion exchange resins, column chromatography, and recrystallization.

[0023] Pteropodine, Isopteropodine, 6-Gingerol, and 6-Shogaol can also be produced by organic chemical synthesis, but are preferably of plant origin. These compounds are obtained by extracting from plants, and it is preferable that the extract solution is recovered by filtration, centrifugation, etc., and then purified by treatments such as concentration, adsorption, separation, elution, and solvent removal. Examples of the plants used for extraction include Uncaria tomentosa and Zingiber officinale. The synthesis method is not particularly limited, and conventionally known methods can be used.

[0024] The structure of the compound obtained by synthesis or purification can be identified according to means known to those skilled in the art. For example, proton nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR), mass spectrometry (MS), elemental analysis, infrared spectroscopy (IR), ultraviolet spectroscopy (UV), melting point measurement, etc. may be used alone or in combination.

[0025] Since the above compounds can also be obtained by extracting and purifying Uncaria tomentosa or Zingiber officinale, the above Uncaria tomentosa extract and Zingiber officinale extract are considered to be usable as a preventive or therapeutic agent for coronavirus disease.

[0026] In addition, in the above compound, the "pharmaceutically acceptable salt" is typically a salt formed by the reaction of the above compound with an acid or a base, and the "pharmaceutically acceptable ether" is typically an ether formed by the reaction of the above compound with an alcohol, an alkoxide, or an organic halogen compound, and refers to those that can maintain the preventive or therapeutic effect of the above compound against coronavirus disease.

[0027] The Uncaria tomentosa extract, Zingiber officinale extract, Pteropodine and its pharmaceutically acceptable salts, Isopteropodin and its pharmaceutically acceptable salts e, 6-Gingerol and its pharmaceutically acceptable ethers, and 6-Shogaol and its pharmaceutically acceptable ethers have excellent preventive and therapeutic effects against coronavirus disease. In particular, they are suitable for being formulated in the food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, and sundries of the present invention described below.

[0028] The food composition is not particularly limited and can be appropriately selected according to the purpose. For example, beverages such as soft drinks, carbonated beverages, nutritional beverages, fruit beverages, lactic acid beverages, etc.; confectioneries such as candies, chocolates, chewing gums, jellies, gums, chocolates, etc.; health foods, foods with function claims, and dietary supplements in various forms such as granules, tablets, capsules, and drinkable agents.

[0029] The pharmaceutical composition is not particularly limited and can be appropriately selected according to the purpose. For example, tablets, capsules, drinkable agents, lozenges, etc.

[0030] The quasi-drug composition is not particularly limited and can be appropriately selected according to the purpose. For example, disinfectants, masks, hand gels, medicinal soaps, gargles, bath salts, medicinal toothpastes, etc.

[0031] The cosmetic composition is not particularly limited and can be appropriately selected according to the purpose. For example, lotions, emulsions, creams, milky lotions, hair styling products, shampoos, finishing cosmetics, etc.

[0032] In addition, miscellaneous goods are not particularly limited and can be appropriately selected according to the purpose. For example, disinfectants, masks, gloves, face shields, hand gels, sprays, wet tissues, air purifiers, aroma oils, soaps, toothpastes, etc.

[0033] The food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, and miscellaneous goods for the prevention or treatment of coronavirus disease are preferably applicable to humans, but can also be applied to animals other than humans as long as the respective effects can be obtained.

[0034] As described above, according to this embodiment, it is possible to provide a food composition, a pharmaceutical composition, a quasi-drug composition, a cosmetic composition, and miscellaneous goods for the prevention or treatment of coronavirus disease, which contain natural products or compounds derived from natural products as components and have high safety and easy availability of raw materials.

Example

[0035] Hereinafter, embodiments of the present invention will be described, but the present invention is not limited to these embodiments at all.

[0036] (Production Example 1) -Isolation and purification of pteropodine- An extract of Uncaria tomentosa manufactured by Tokiwa Phytochemical Co., Ltd. is subjected to heat extraction under sulfuric acid acidic conditions. After adjusting the pH to neutral, an equal volume of a methanol / chloroform mixture is added, and liquid-liquid partitioning is performed, followed by column purification using silica gel. The fraction rich in pteropodine is concentrated and dried, adsorbed again onto a column packed with silica gel, eluted using a hexane / ethyl acetate mixture, and then recrystallized to obtain pteropodine. The structure is shown in Chemical Formula (1). [Chemical formula]

[0037] <1H-NMR (500 MHz, CDCl3)> δ 1.40 (3H, d, J = 6.1 Hz, 18-CH3), 1.51 (1H, m, 14β-H), 1.59 (1H, m, 20-H), 1.72 (1H, ddd, J = 12.1 Hz, J = 4.3 Hz, J = 4.3 Hz, 14α-H), 1.99 (1H, m, 6α-H), 2.32 (1H, dd, J = 12.1 Hz, J = 3.8 Hz, 21α-H), 2.36 (1H, dd, J = 12.1 Hz, J = 4.3 Hz, 3-H), 2.36 (1H, m, 5α-H), 2.40 (1H, ddd, J = 13.0 Hz, J = 12.5 Hz, 6β-H), 2.44 (1H, ddd, J = 12.1 Hz, J = 4.7 Hz, J = 4.3 Hz, 15-H), 3.30 (1H, ddd, J = 13.0 Hz, J = 8.5 Hz, J = 2.9 Hz, 5β-H), 3.32 (1H, dd, J = 12.1 Hz, J = 2.0 Hz, 21β-H), 3.60 (3H, s, 23-OCH3), 4.55 (1H, qd, J = 10.5 Hz, J = 6.1 Hz, 19-H), 6.87 (1H, d, J = 7.6 Hz, 12-H), 7.04 (1H, ddd, J = 7.6 Hz, J = 7.3 Hz, J = 1.0 Hz, 10-H), 7.18 (1H, ddd, J = 7.6 Hz, J = 7.6 Hz, J = 1.2 Hz, 11-H), 7.20 (1H, d, J = 7.3 Hz, 9-H), 7.41 (1H, s, 17-H), 8.52 (1H, brs, NH)

[0038] (Production Example 2) -Isolation and Purification of Isopteropodine- The extract of Uncaria tomentosa manufactured by Tokiwa Phytochemical Co., Ltd. is subjected to heat extraction under sulfuric acid acidic conditions. After adjusting the pH to neutral, an equal volume of a methanol / chloroform mixed solution is added, followed by liquid-liquid partitioning, and then column purification using silica gel is performed. After concentrating and drying the hexane / ethyl acetate elution fraction, column purification using silica gel is performed again. After eluting with a hexane / ethyl acetate mixed solution, recrystallization is carried out to obtain Isopteropodine. The structure is shown in Chemical Formula (2). [Chemical Formula]

[0039] <1H-NMR (500 MHz, CDCl3)> δ 0.88 (1H, ddd, J = 11.7 Hz, J = 11.7 Hz, J = 11.7 Hz, 14β-H), 1.41 (3H, d, J = 6.2 Hz, 18-CH3), 1.59 (1H, m, 20-H), 1.62 (1H, ddd, J = 11.7 Hz, J = 2.8 Hz, J = 2.8 Hz, 14α-H), 2.00 (1H, ddd, J = 11.9 Hz, J = 7.6 Hz, J = 7.6 Hz, 6α-H), 2.39 (1H, ddd, J = 11.9 Hz, J = 7.6 Hz, J = 2.4 Hz, 6β-H), 2.42 (1H, dd, J = 11.9 Hz, J = 3.8 Hz, 21-α), 2.46 (1H, ddd, J = 7.6 Hz, J = 7.6 Hz, J = 7.6 Hz, 5α-H), 2.51 (1H, ddd, J = 11.7 Hz, J = 2.8 Hz, J = 2.8 Hz, 15-H), 2.57 (1H, dd, J = 11.7 Hz, J = 2.8 Hz, 3-H), 3.22 (1H, ddd, J = 7.6 Hz, J = 7.6 Hz, J = 2.4 Hz, 5β-H), 3.29 (1H, dd, J = 11.9 Hz, J = 1.8 Hz, 21β-H), 3.60 (3H, s, 23-OCH3), 4.36 (1H, qd, J = 10.4 Hz, J = 6.2 Hz, 19-H), 6.89 (1H, d, J = 7.7 Hz, 12-H), 7.02 (1H, ddd, J = 7.7 Hz, J = 7.7 Hz, J = 1.1 Hz, 10-H), 7.19 (1H, ddd, J = 7.7 Hz, J = 7.7 Hz, J = 1.3 Hz, 11-H), 7.27 (1H, d, J = 7.7 Hz, 9-H), 7.41 (1H, s, 17-H), 8.42 (1H, brs, NH)

[0040] (Production Example 3) - Isolation and Purification of 6-Gingerol - Methanol was added to the dried and pulverized ginger (Zingiber officinale) for extraction, and after concentration, water and diethyl ether were added to the concentrated solution for liquid-liquid partitioning. After concentrating the diethyl ether layer, column purification using silica gel was performed. After eluting with hexane, a hexane / ethyl acetate mixture, and methanol, the fraction rich in 6-Gingerol was concentrated, and further purification was carried out with 75% methanol using reverse-phase high-performance liquid chromatography (ODS) to obtain 6-Gingerol. The structure is shown in Chemical Formula (3).

Chem.

[0041] <1H-NMR(500MHz,CDCl3)> δ0.89(3H,t,J = 7.0Hz,10-CH3), 1.30(6H,m,7-2H,8-2H,9-2H), 1.38 - 1.49(2H,m,6-2H), 2.48(1H,dd,J = 17.5Hz,J = 9.0Hz,4-H), 2.57(1H,dd,J = 17.5Hz,J = 2.0Hz,4-H), 2.73(2H,m,2-2H), 2.84(2H,m,1-2H), 3.87(3H,s,3’-OCH3), 4.02(1H,m,5-H), 6.66(1H,dd,J = 8.0Hz,J = 2.0Hz,6’-H), 6.68(1H,d,J = 2.0Hz,2’-H), 6.82(1H,d,J = 8.0Hz,5’-H)

[0042] (Production Example 4) - Isolation and Purification of 6-Shogaol - Methanol was added to the dried and pulverized ginger (Zingiber officinale) for extraction, and after concentration, water and diethyl ether were added to the concentrated solution for liquid-liquid partitioning. After concentrating the diethyl ether layer, column purification using silica gel was performed. After eluting with hexane, a hexane / ethyl acetate mixture, and methanol, the fraction rich in 6-Shogaol was concentrated, and further purification was carried out with 35% acetonitrile using reverse-phase high-performance liquid chromatography (ODS) to obtain 6-Shogaol. The structure is shown in Chemical Formula (4). [Chemical formula]

[0043] <1H-NMR(600MHz,CDCl3)> δ0.89(3H,t,J = 8.7Hz,10-CH3), 1.30(4H,m,8-2H,9-2H), 1.45(2H,m,7-2H), 2.19(1H,ddd,J = 16.2Hz,J = 10.8Hz,J = 1.8Hz,6-H), 2.85(4H,m,1-2H,2-2H), 3.87(3H,s,3’-OCH3), 6.09(1H,br d,J = 19.2Hz,4-H), 6.68(1H,dd,J = 9.6Hz,2.4Hz,6’-H), 6.71(1H,d,J = 2.4Hz,2’-H), 6.80(1H,m,5-H), 6.83(1H,d,J = 9.6Hz,5’-H)

[0044] (Example 1) - Inhibitory effect on the infection of novel coronavirus - Using the compounds of Production Examples 1 to 4 as samples, the inhibitory effect on the infection of novel coronavirus was evaluated by the following test method.

[0045] Added to the VeroE6 / TMPRSS2 cell medium at a final concentration of 10 μM and cultured at 37°C for 3 hours. Then, novel coronavirus SARS-CoV-2 (MOI = 0.05) was added to infect the cells. Further cultured at 37°C for 48 hours, and CellTiter-Glo TM was added to measure the cell viability. As positive controls, camostat and nafamostat, which have been reported to be able to inhibit the infection of novel coronavirus to lung cells, were used.

[0046] From the results in Figure 1, it was confirmed that the compounds of Production Examples 1 to 4 have a higher inhibitory effect on the infection of novel coronavirus than the positive controls camostat and nafamostat.

[0047] In addition, the IC50 values of Production Examples 2 to 4 were calculated using the cell viability of VeroE6 / TMPRSS2 cells as an index. [Table 1]

[0048] (Example 2) Viral infection was visualized by performing immunostaining with an antibody against SARS-CoV-2 N protein. Production Examples 2 and 3 were added to the medium of VeroE6 / TMPRSS2 cells at final concentrations of 10 μM, 25 μM, and 50 μM, and cultured at 37°C for 3 hours. Then, the novel coronavirus SARS-CoV-2 (MOI = 0.05) was added to infect the cells. The cells were further cultured at 37°C for 24 hours and fixed with 4% paraformaldehyde. Triton X-100 was added for permeabilization and treated at room temperature for 15 minutes. Then Blocking One TM was used for blocking treatment at room temperature for 15 minutes. For immunostaining, SARS-CoV-2 Nucleocapsid Protein antibody (1:100 dilution, Novus NB100-56576) was used to react at room temperature for 1 hour, and then Alexa 568-labeled anti-rabbit antibody (1:100 dilution, Thermo) was used for staining at room temperature for 1 hour. The nuclei of the cells were stained using Prolong Gold Antifade Mount with DAPI (Thermo).

[0049] From the results in Figure 2, when Production Examples 2 and 3 were added, a concentration-dependent decrease in infected cells was observed in both cases.

[0050] (Example 3) The inhibitory effect on SARS-CoV-2 infection was examined to determine whether it acts on cell entry or after cell entry. Manufacture Examples 2 and 3 with a final concentration of 50 μM were added to the medium of VeroE6 / TMPRSS2 cells under the following conditions. Under the Full time condition, they were added to the medium 3 hours before infection with the novel coronavirus SARS-CoV-2 (MOI = 0.05), and after washing 2 hours after infection, Manufacture Examples 2 and 3 were present in the medium at 50 μM. Under the Entry condition, they were added to the medium 3 hours before infection with the novel coronavirus SARS-CoV-2 (MOI = 0.05), and were present in the medium until after washing 2 hours after infection. Under the Post-entry condition, Manufacture Examples 2 and 3 were present from after washing 2 hours after infection with the novel coronavirus SARS-CoV-2 (MOI = 0.05) until detection 48 hours after infection. Detection was performed 48 hours after infection by adding TM CellTiter-Glo to measure cell viability.

Table 2

[0051] From the results in Figure 3, it was confirmed that both Manufacture Examples 2 and 3 act after cell entry.

[0052] (Example 4) After the polyprotein is synthesized, the coronavirus synthesizes functional peptides by being cleaved at three positions by a papain-like enzyme and then cleaved at 11 positions by 3CL protease. Using a test system capable of detecting the cleavage reaction of the polyprotein by protease by Western blotting, the inhibitory effect on the cleavage of the polyprotein by protease was examined. Using a wheat germ cell-free protein synthesis system, the novel coronavirus SARS-CoV-2 3CL protease and a peptide having an amino acid sequence cleaved by 3CL protease (FLAG-TSITSAVLQ^SGFRKMAFP-GST-biotin) were synthesized. The synthesized protease and substrate, and further Manufacture Examples 2 and 3 at a final concentration of 500 μM were added, reacted at 37 °C for 3 hours, subjected to SDS-PAGE using a 13% polyacrylamide gel and transferred to a PVDF membrane, and Blocking One TMBlocking treatment was performed at room temperature for 15 minutes. Then, detection was carried out using anti-streptavidin-HRP antibody (1:5000 dilution).

[0053] From the results of Figure 4, both Production Examples 2 and 3 inhibited the cleavage of polyprotein by protease.

Industrial Applicability

[0054] The present invention has industrial applicability as a food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, or miscellaneous goods, which is formulated with at least any one of cat's claw extract, ginger extract, pteropodine and its pharmaceutically acceptable salts, isopteropodine and its pharmaceutically acceptable salts, 6-gingerol and its pharmaceutically acceptable ethers, and 6-shogaol and its pharmaceutically acceptable ethers as an active ingredient.

Claims

**Claim 1** A prophylactic or therapeutic agent for coronavirus disease, which contains an extract of Zingiber officinale extracted with 10% to 95% aqueous ethanol in a temperature range of 4 to 90°C, for preventing or treating after the cell invasion of the novel coronavirus. **Claim 2** A prophylactic or therapeutic agent for coronavirus disease, which contains at least one of Pteropodine isolated and purified from cats claw or organically chemically synthesized, and a pharmaceutically acceptable salt thereof, for preventing or treating after the cell invasion of the novel coronavirus. **Claim 3** A prophylactic or therapeutic agent for coronavirus disease, which contains at least one of Isopteropodine isolated and purified from cats claw or organically chemically synthesized, and a pharmaceutically acceptable salt thereof, for preventing or treating after the cell invasion of the novel coronavirus. **Claim 4** A prophylactic or therapeutic agent for coronavirus disease, which contains at least one of 6-Gingerol isolated and purified from ginger or organically chemically synthesized, and a pharmaceutically acceptable ether thereof, for preventing or treating after the cell invasion of the novel coronavirus. **Claim 5** A prophylactic or therapeutic agent for coronavirus disease, which contains at least one of 6-Shogaol isolated and purified from ginger or organically chemically synthesized, and a pharmaceutically acceptable ether thereof, for preventing or treating after the cell invasion of the novel coronavirus. **Claim 6** A food composition, a pharmaceutical composition, or a quasi-drug composition for preventing or treating after the cell invasion of the novel coronavirus, which contains at least one of the extracts or compounds described in Claims 1 to 5.

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