JP7691691B2 - Food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, and miscellaneous goods for the prevention or treatment of COVID-19 - Google Patents

Description

The present invention relates to a food composition, a pharmaceutical composition, a quasi-drug composition, a cosmetic composition, and miscellaneous goods for preventing or treating COVID-19.

COVID-19 was first confirmed in Wuhan, Hubei Province, China in December 2019, and has since spread to various parts of the world. The novel coronavirus (SARS-CoV-2), which causes the disease, is a type of coronavirus and a positive-stranded RNA virus belonging to the Coronaviridae subfamily of the Coronaviridae family. Coronaviruses are not only the cause of the common cold, but also include the viruses that caused Severe Acute Respiratory Syndrome (SARS), which was prevalent mainly in Asia in 2003, and Middle East Respiratory Syndrome (MERS), which has been spreading in the Middle East since 2012. The main symptoms of COVID-19 are fever, general fatigue, and respiratory symptoms. Approximately 80% of cases are cured with mild symptoms, but approximately 20% of cases will develop worsening pneumonia symptoms, and approximately 5% will become severe cases requiring artificial respiration management, and there have been reports of sudden deterioration of the condition. One factor that is thought to cause the disease to worsen is an excessive immune response caused by a cytokine storm, which is an excessive release of cytokines from immune cells, which causes damage to organs such as the lungs.

As of the filing date of this application, there is no specific treatment for COVID-19, and existing drugs have only been repurposed. The anti-Ebola virus drug remdesivir has been confirmed to be effective in shortening the treatment period for severe COVID-19 patients, and has received special approval in Japan. However, the drug is generally administered to severely ill patients, and there are safety concerns, such as the high incidence of renal and liver dysfunction. In addition, there is also the issue that the supply of remdesivir is limited. In addition, it has been reported that the steroid drug dexamethasone has reduced the death rate in severe cases, and it is the second drug approved in Japan for use as a treatment for COVID-19. However, the US NIH treatment guidelines recommend its use for severely ill patients, and no treatment has been established for those with mild symptoms. Other treatments are used off-label, and their effectiveness and safety are unclear as they are still in the process of being verified. In addition, although some vaccines have begun clinical trials as a generally effective means of preventing viral infection, they have not yet been put to practical use. Given this current situation, the development of preventive and therapeutic agents that are effective against COVID-19 and can be supplied stably and safely is an urgent issue.

On the other hand, there have been reports using molecular docking methods on the interactions between naturally derived ingredients and novel coronavirus (SARS-CoV-2) proteins, and it has been shown that epigallocatechin gallate, anthocyanidins, curcumin, etc. may have antiviral effects (Non-Patent Documents 1 and 2).

Preprint, DOI: 10.26434/chemrxiv. 12051927. v2 Preprint, DOI: 10.21203/rs. 3. rs-19560/v

However, these are the results of computer simulations, and their effectiveness has not been demonstrated at the cellular or animal level. As mentioned above, there are safety concerns about the therapeutic drugs currently in use, and supplies are limited, so there is a demand for preventive or therapeutic food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, and miscellaneous goods that use natural products that are highly safe and from which the raw materials are easily available, and that can solve these issues.

The present invention aims to solve the above-mentioned problems in the past and achieve the following objectives. That is, the present invention aims to provide a food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, and miscellaneous goods for preventing or treating COVID-19 infection, which contain natural products that are highly safe and the raw materials of which are easily available.

In order to solve the above problems, the inventors conducted extensive research into a preventive or therapeutic agent for COVID-19 that is a highly safe natural product and can be widely used in foods, medicines, quasi-drugs, cosmetics, and miscellaneous goods, and as a result, they arrived at the present invention.

That is, the present invention relates to a food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, or miscellaneous goods that contain at least one of cat's claw extract, ginger extract, pteropodine and a pharma- ceutically acceptable salt thereof, isopteropodine and a pharma- ceutically acceptable salt thereof, 6-gingerol and a pharma- ceutically acceptable ether thereof, and 6-shogaol and a pharma- ceutically acceptable ether thereof, preferably as an active ingredient, and have a preventive or therapeutic effect against the novel coronavirus. Up to now, the effects of cat's claw extract, ginger extract, pteropodine, isopteropodine, 6-gingerol, and 6-shogaol against the novel coronavirus were completely unknown, and this is a new finding made by the inventors through intensive research.

More specifically, the present invention is as follows. That is, a preventive or therapeutic agent for COVID-19 according to one aspect of the present invention contains cat's claw (Uncaria tomentosa) extract, which is preferably formulated as an active ingredient. Here, the "agent" in preventive agent and therapeutic agent is a term used as a counter, and is used to mean something that has a pharmacological function, but this does not necessarily mean a pharmaceutical composition (drug), and this preventive agent and therapeutic agent can be used as an active ingredient in a food composition, pharmaceutical composition, quasi-drug composition, cosmetic composition, or miscellaneous goods.

In addition, a preventive or therapeutic agent for COVID-19 according to another aspect of the present invention contains ginger (Zingiber officinale) extract, and preferably contains this as an active ingredient.

In addition, a preventive or therapeutic agent for COVID-19 according to another aspect of the present invention contains at least one of pteropodine and a pharma- ceutically acceptable salt thereof, and preferably contains this as an active ingredient.

In addition, a preventive or therapeutic agent for COVID-19 according to another aspect of the present invention contains at least one of isopteropodine and a pharma- ceutically acceptable salt, and preferably contains this as an active ingredient.

In addition, a preventive or therapeutic agent for COVID-19 according to another aspect of the present invention contains at least one of 6-gingerol and a pharma- ceutically acceptable ether, and preferably contains this as an active ingredient.

In addition, a pharmaceutical composition for preventing or treating COVID-19 infection according to another aspect of the present invention contains at least one of 6-Shogaol and a pharma- ceutical acceptable ether, and preferably contains this as an active ingredient.

As described above, the present invention can provide food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, and miscellaneous goods for preventing or treating COVID-19 infection, which contain natural products that are highly safe and from which the raw materials are easily available. The present invention is a naturally derived extract or compound that is highly safe and therefore suitable for use as a blend or addition to foods, pharmaceuticals, quasi-drugs, cosmetics, and miscellaneous goods.

A brief explanation of the figures in the embodiments is as follows.
This shows the inhibitory effect of Production Examples 1 to 4 on novel coronavirus infection. FIG. 1 shows the results of immunostaining using an antibody against SARS-CoV-2 Nprotein. Graph showing confirmation of the infection suppression effect against SARS-CoV-2. FIG. 1 shows the results regarding the inhibitory effect on the cleavage of polyproteins by proteases.

The following describes in detail the embodiments of the present invention. The present invention can be implemented in many different forms, and is not limited to the specific examples of the embodiments and examples shown below.

The preventive or therapeutic agent for COVID-19 of the present invention contains at least one of cat's claw extract, ginger extract, pteropodine and its pharma- ceutically acceptable salt, isopteropodine and its pharma- ceutically acceptable salt, 6-gingerol and its pharma- ceutically acceptable ether, and 6-shogaol and its pharma- ceutically acceptable ether, and preferably contains at least one of these as an active ingredient, and further contains other ingredients as necessary.

The cat's claw extract and ginger extract can be easily obtained by methods commonly used for plant extraction. Each plant extract includes the extract of the raw material for extraction, a dried product obtained by drying a diluted solution of the extract, or a crude or purified product thereof. The parts of the raw material for extraction are not limited as long as the above-mentioned effects can be obtained, but it is preferable to use the bark for cat's claw extract and the rhizome for ginger extract.

The method for extracting the above-mentioned plant extract is not particularly limited, and can be carried out according to a method 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 can be used alone or in combination. Among these, it is preferable to use ethanol, and it is more preferable to use aqueous ethanol with an ethanol content of 10% to 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 exhibiting the above-mentioned effects can be obtained. The amount of the extraction solvent is preferably 1 to 100 parts by weight based on the dry weight of the raw material. The extraction temperature is preferably 4 to 90°C. The extraction time is preferably 30 minutes to 1 week. The extraction method can be any method such as stirring extraction, immersion extraction, countercurrent extraction, ultrasonic extraction, and supercritical extraction.

The above extract may be the filtrate itself obtained by filtering the extract obtained, a concentrate obtained by concentrating the filtrate, a dried product obtained by drying the concentrate, or a crude or purified product thereof. The concentration and drying methods may be any method. If necessary, excipients such as dextrin may be added. Purification may be performed according to means known to those skilled in the art, such as synthetic adsorption resins, activated carbon, ion exchange resins, column chromatography, and recrystallization.

Pteropodine, Isopteropodine, 6-Gingerol, and 6-Shogaol can be produced by organic chemical synthesis, but it is preferable that they are derived from plants. These compounds are obtained by extraction from plants, and the extract is recovered by filtration or centrifugation, and then purified by processes such as concentration, adsorption, separation, elution, and solvent removal. Examples of plants used for extraction include cat's claw (Uncaria tomentosa) and ginger (Zingiber officinale). The synthesis method is not particularly limited, and conventionally known methods can be used.

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.

The above compounds can also be obtained by extracting and purifying cat's claw (Uncaria tomentosa) and ginger (Zingiber officinale), so it is believed that the above cat's claw extract and ginger extract can also be used as a preventive or therapeutic agent for COVID-19.

In addition, in the above compounds, a "pharmaceutical acceptable salt" is typically a salt produced by reacting the above compounds with an acid or a base, and a "pharmaceutical acceptable ether" is typically an ether produced by reacting the above compounds with an alcohol, an alkoxide, or an organic halogen compound, which is capable of maintaining the effect of the above compounds in preventing or treating COVID-19.

Cat's claw extract, ginger extract, pteropodine and its pharma- ceutically acceptable salts, isopteropodin and its pharma- ceutically acceptable salts, 6-gingerol and its pharma- ceutically acceptable ethers, and 6-shogaol and its pharma- ceutically acceptable ethers have excellent prophylactic and therapeutic effects against COVID-19. They are particularly suitable for incorporation into the food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, and miscellaneous goods of the present invention described below.

There are no particular limitations on the food composition, and it can be appropriately selected depending on the purpose. Examples include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks; confectioneries such as candies, chewables, jellies, gums, and chocolates; health foods in various forms such as granules, tablets, capsules, and drinks, functional foods, and nutritional supplements.

There are no particular limitations on the pharmaceutical composition, and it can be appropriately selected depending on the purpose, but examples include tablets, capsules, drinks, and lozenges.

There are no particular limitations on the quasi-drug composition and it can be selected appropriately depending on the purpose, but examples include disinfectants, masks, hand gels, medicated soaps, mouthwashes, bath additives, medicated toothpaste, etc.

There are no particular limitations on the cosmetic composition and it can be selected appropriately depending on the purpose, but examples include lotions, cosmetic liquids, creams, milky lotions, hair styling products, hair washes, finishing cosmetics, etc.

There are no particular limitations on the miscellaneous goods, and they can be selected appropriately depending on the purpose, but examples include disinfectants, masks, gloves, face shields, hand gels, sprays, wet tissues, air purifiers, aroma oils, soap, toothpaste, etc.

Food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, and miscellaneous goods for preventing or treating COVID-19 are preferably applied to humans, but can also be applied to animals other than humans as long as their respective functional effects can be obtained.

As described above, this embodiment can provide food compositions, pharmaceutical compositions, quasi-drug compositions, cosmetic compositions, and miscellaneous goods for preventing or treating COVID-19 infection, which contain natural products or compounds derived from natural products that are highly safe and whose raw materials are easily available.

The following describes examples of the present invention, but the present invention is not limited to these examples.

(Production Example 1)
-Isolation and purification of pteropodine-
Cat's claw (Uncaria tomentosa) extract manufactured by Tokiwa Phytochemical Laboratory Co., Ltd. was heated and extracted under acidic conditions using sulfuric acid. After adjusting the pH to neutral, an equal amount of a methanol/chloroform mixture was added to perform liquid-liquid distribution, followed by column purification using silica gel. The fraction containing a large amount of pteropodine was concentrated and dried, and again adsorbed onto a column packed with silica gel. After elution with a hexane/ethyl acetate mixture, the fraction was recrystallized to obtain pteropodine. The structure is shown in chemical formula (1).

<1H-NMR (500MHz, CDCl3)>
δ1.40 (3H, d, J = 6.1Hz, 18-CH3), 1.51 (1H, m, 14β-H), 1.59 (1H, m, 20-H), 1.72 (1H, ddd, J=12.1Hz, J=4.3Hz, J=4.3Hz, 14α-H), 1.99 (1H, m, 6α-H), 2.32 (1H, dd, J=12.1Hz, J=3. 8Hz, 21α-H), 2.36 (1H, dd, J = 12.1Hz, J = 4.3Hz, 3-H), 2.36 (1H, m, 5α-H), 2.40 (1H, ddd, J=13.0Hz, J=12.5Hz, 6β-H), 2.44 (1H, ddd, J=12.1Hz, J=4.7Hz, J=4.3Hz, 15-H), 3.30( 1H, dd, J=13.0Hz, J=8.5Hz, J=2.9Hz, 5β-H), 3.32 (1H, dd, J=12.1Hz, J=2.0Hz, 21β-H) , 3.60 (3H, s, 23-OCH3), 4.55 (1H, qd, J = 10.5Hz, J = 6.1Hz, 19-H), 6.87 (1H, d, J = 7.6Hz, 12-H), 7.04 (1H, ddd, J=7.6Hz, J=7.3Hz, J=1.0Hz, 10-H), 7.18 (1H, ddd, J=7.6Hz, J=7. 6Hz, J=1.2Hz, 11-H), 7.20 (1H, d, J=7.3Hz, 9-H), 7.41 (1H, s, 17-H), 8.52 (1H, brs, NH)

(Production Example 2)
-Isolation and purification of isopteropodine-
Cat's claw (Uncaria tomentosa) extract manufactured by Tokiwa Phytochemical Laboratory Co., Ltd. was heated and extracted under acidic conditions using sulfuric acid. After adjusting the pH to neutral, an equal amount of a methanol/chloroform mixture was added to carry out liquid-liquid distribution, followed by column purification using silica gel. The hexane/ethyl acetate eluted fraction was concentrated and dried, and then column purification using silica gel was carried out again. After elution with a hexane/ethyl acetate mixture, the fraction was recrystallized to obtain Isopteropodine. The structure is shown in chemical formula (2).

<1H-NMR (500MHz, CDCl3)>
δ0.88 (1H, ddd, J=11.7Hz, J=11.7Hz, J=11.7Hz, 14β-H), 1.41 (3H, d, J=6.2Hz, 18-CH3), 1.59 (1H, m , 20-H), 1.62 (1H, ddd, J=11.7Hz, J=2.8Hz, J=2.8Hz, 14α-H), 2.00 (1H, ddd, J=11.9Hz, J=7.6Hz, J=7 ．． 6Hz, 6α-H), 2.39 (1H, dd, J = 11.9Hz, J = 7.6Hz, J = 2.4Hz, 6β-H), 2.42 (1H, dd, J = 11.9Hz, J = 3.8Hz, 2 1-α), 2.46 (1H, ddd, J=7.6Hz, J=7.6Hz, J=7.6Hz, 5α-H), 2.51 (1H, ddd, J=11.7Hz, J=2.8Hz, J=2.8Hz , 15-H), 2.57 (1H, dd, J = 11.7Hz, J = 2.8Hz, 3-H), 3.22 (1H, ddd, J = 7.6Hz, J = 7.6Hz, J = 2.4Hz, 5β-H), 3 .29 (1H, dd, J=11.9Hz, J=1.8Hz, 21β-H), 3.60 (3H, s, 23-OCH3), 4.36 (1H, qd, J=10.4Hz, J=6.2Hz, 19 -H), 6.89 (1H, d, J = 7.7Hz, 12-H), 7.02 (1H, ddd, J = 7.7Hz, J = 7.7Hz, J = 1.1Hz, 10-H), 7.19 (1H, ddd, J =7.7Hz, J=7.7Hz, J=1.3Hz, 11-H), 7.27 (1H, d, J=7.7Hz, 9-H), 7.41 (1H, s, 17-H), 8.42 (1H, brs, NH)

(Production Example 3)
-Isolation and purification of 6-gingerol-
Methanol was added to dried ginger (Zingiber officinale) powder, extracted, and concentrated. Water and diethyl ether were added to the concentrate to perform liquid-liquid distribution. The diethyl ether layer was concentrated and then purified using a column of silica gel. After elution with hexane, a hexane/ethyl acetate mixture, and methanol, the fraction containing a large amount of 6-gingerol was concentrated and further purified with 75% methanol using reversed-phase high performance liquid chromatography (ODS) to obtain 6-gingerol. The structure is shown in chemical formula (3).

<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, 6-2 H), 2.48 (1H, dd, J=17.5Hz, J=9.0Hz, 4-H), 2.57 (1H, dd, J=17.5Hz, J=2.0Hz, 4-H), 2.7 3 (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)

(Production Example 4)
-Isolation and purification of 6-Shogaol-
Methanol was added to dried ground ginger (Zingiber officinale) and extracted. The extract was concentrated, and then water and diethyl ether were added to the concentrate to carry out liquid-liquid distribution. The diethyl ether layer was concentrated and then purified using a column of silica gel. After elution with hexane, a mixture of hexane/ethyl acetate, and methanol, the fraction containing a large amount of 6-Shogaol was concentrated and further purified with 35% acetonitrile using reversed-phase high performance liquid chromatography (ODS) to obtain 6-Shogaol. Its structure is shown in chemical formula (4).

<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)

Example 1
- Effective in suppressing the spread of COVID-19 -
The compounds of Production Examples 1 to 4 were used as samples to evaluate their inhibitory effect on novel coronavirus infection by the following test method.

The cells were added to the VeroE6/TMPRSS2 cell medium at a final concentration of 10 μM and cultured at 37°C for 3 hours. Then, the new coronavirus SARS-CoV-2 (MOI = 0.05) was added to infect the cells. The cells were further cultured at 37°C for 48 hours, and CellTiter-Glo ^TM was added to measure cell viability.
The positive controls used were Camostat and Nafamostat, which have been reported to be able to suppress infection of lung cells by the new coronavirus.

From the results in Figure 1, it was confirmed that the compounds of Production Examples 1 to 4 have a higher infection suppression effect against the new coronavirus than the positive control compounds Camostat and Nafamostat.

The IC50 values of Production Examples 2 to 4 were calculated using the cell viability of VeroE6/TMPRSS2 cells as an index.

Example 2
Viral infection was visualized by immunostaining using an antibody against SARS-CoV-2 Nprotein.
Production Example 2 and Production Example 3 were added to the medium of VeroE6/TMPRSS2 cells at final concentrations of 10 μM, 25 μM, and 50 μM, and after culturing at 37 ° C for 3 hours, the new coronavirus SARS-CoV-2 (MOI = 0.05) was added and the cells were infected. The cells were further cultured at 37 ° C for 24 hours, and fixed with 4% paraformaldehyde. Triton X-100 was added as a permeabilization treatment, and the treatment was performed at room temperature for 15 minutes. Then, blocking treatment was performed at room temperature for 15 minutes with Blocking One ^TM . Immunostaining was performed using SARS-CoV-2 Nucleocapsid Protein antibody (1:100 dilution, Novus NB100-56576) at room temperature for 1 hour, followed by staining with Alexa 568-labeled anti-rabbit antibody (1:100 dilution, Thermo) at room temperature for 1 hour. Cell nuclei were stained using Prolong Gold Antifade Mount with DAPI (Thermo).

The results in Figure 2 show that when Production Examples 2 and 3 were added, a concentration-dependent decrease in the number of infected cells was observed.

Example 3
We investigated whether the inhibitory effect on SARS-CoV-2 infection occurs during or after cell entry.
Production Examples 2 and 3 were added to the medium of VeroE6/TMPRSS2 cells at a final concentration of 50 μM under the following conditions. Under the full-time conditions, they were added to the medium 3 hours before infection with the new coronavirus SARS-CoV-2 (MOI = 0.05), and Production Examples 2 and 3 were present in the medium at 50 μM even after washing 2 hours after infection. Under the entry conditions, they were added to the medium 3 hours before infection with the new coronavirus SARS-CoV-2 (MOI = 0.05), and Production Examples 2 and 3 were present in the medium until washing 2 hours after infection. Under the post-entry conditions, Production Examples 2 and 3 were present from washing 2 hours after infection with the new coronavirus SARS-CoV-2 (MOI = 0.05) until detection 48 hours after infection. For detection, CellTiter-Glo ^TM was added 48 hours after infection to measure cell viability.

The results in Figure 3 confirm that both Preparations 2 and 3 act after cell entry.

Example 4
After synthesizing the polyprotein, coronaviruses synthesize functional peptides by cleaving it at three sites with a papain-like enzyme and then cleaving it at 11 sites with 3CL protease.
Using a test system that can detect the cleavage reaction of polyprotein by proteases by Western blot analysis, the inhibitory effect on the cleavage of polyprotein by proteases was examined.
Using a wheat cell-free protein synthesis system, the novel coronavirus SARS-CoV-2 3CL protease and a peptide having an amino acid sequence cleaved by the 3CL protease (FLAG-TSITSAVLQ^SGFRKMAFP-GST-biotin) were synthesized. The synthesized protease and substrate, as well as Production Examples 2 and 3 were added at a final concentration of 500 μM, and reacted at 37 ° C for 3 hours, and SDS-PAGE was performed using a 13% polyacrylamide gel, transferred to a PVDF membrane, and blocked with Blocking One ^TM at room temperature for 15 minutes. Detection was then performed using anti-streptavidin-HRP antibody (1:5000 dilution).

The results in Figure 4 show that both Production Examples 2 and 3 inhibited the cleavage of polyprotein by proteases.

The present invention has industrial applicability as a food composition, a pharmaceutical composition, a quasi-drug composition, a cosmetic composition, or a miscellaneous item that contains at least one of cat's claw extract, ginger extract, pteropodine and its pharma- ceutical acceptable salt, isopteropodine and its pharma-ceutical acceptable salt, 6-gingerol and its pharma-ceutical acceptable ether, and 6-shogaol and its pharma-ceutical acceptable ether as an active ingredient.

Claims (6)

A preventive or therapeutic agent for COVID-19, for preventing or treating the COVID-19 virus after it invades cells, comprising a ginger (Zingiber officinale) extract extracted with 10% to 95% aqueous ethanol at a temperature range of 4 to 90°C. A preventive or therapeutic agent for novel coronavirus infection, which contains at least one of pteropodine isolated and purified from cat's claw or organically synthesized, and a pharma- ceutically acceptable salt thereof, for preventing or treating the novel coronavirus after it invades cells. A preventive or therapeutic agent for COVID-19, which contains at least one of isopteropodine isolated and purified from cat's claw or organically synthesized, and a pharma- ceutically acceptable salt, for preventing or treating COVID-19 after the virus invades cells. A preventive or therapeutic agent for COVID-19, which contains at least one of 6-gingerol isolated and purified from ginger or organically synthesized, and a pharma- ceutically acceptable ether, for preventing or treating COVID-19 after the virus invades cells. A preventive or therapeutic agent for COVID-19, which contains at least one of 6-Shogaol isolated and purified from ginger or organically synthesized, and a pharma- ceutically acceptable ether, for preventing or treating COVID-19 after the virus invades cells. A food composition, pharmaceutical composition, or quasi-drug composition for preventing or treating the novel coronavirus after cell invasion, comprising at least one of the extracts or compounds described in claims 1 to 5 .