Antiviral agent

Abstract

The present invention aims to provide a novel antiviral agent.SOLUTION: An anti-viral agent comprising, as an active ingredient, at least one selected from the group consisting of nymphaeol-A, nymphaeol-B, nymphaeol-C, isonymphaeol-B, and 3 ' - geranylnaringenin, or propolis originating from Macaranga.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an antiviral agent, more specifically to an antiviral agent containing at least one active ingredient selected from the group consisting of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin, and an antiviral agent containing propolis derived from a plant of the genus Macaranga as an active ingredient. [Background technology]

[0002] Non-Patent Document 1 reports the virucidal effect of echinacea against SARS-CoV-2 (novel coronavirus). Additionally, Non-Patent Document 2 describes that remdesivir, a drug for treating SARS-CoV-2 infection, inhibits the replication of SARS-CoV-2. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Signer et al, Virology Journal, 2020 Sep 9;17(1):136. [Non-patent document 2] Richard et al,ACS Central Science,2020,6,672-683 Summary of the Invention [Problem to be solved by the invention]

[0004] An object of the present invention is to provide a novel antiviral agent. [Means for solving the problem]

[0005] The present inventors have conducted extensive research to achieve the above-mentioned object and have found that propolis, derived from the genus Macaranga, and the prenylflavonoids characteristically contained in said propolis have excellent antiviral effects, thereby completing the present invention.

[0006] That is, the present invention relates to, for example, the following [1] to [5]. [1] An antiviral agent comprising, as an active ingredient, at least one selected from the group consisting of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin. [2] An antiviral agent containing propolis, derived from the Macaranga genus of plants, as an active ingredient. [3] An antiviral agent according to [1] or [2] against SARS-CoV-2. [4] The antiviral agent according to [1] or [2], which is used against at least one virus selected from the group consisting of influenza virus, viruses belonging to the Caliciviridae family, Sendai virus, and vaccinia virus. [5] The antiviral agent according to any one of [1] to [4], which is a food composition, a cosmetic, a disinfectant, a cleaning agent, or a quasi-drug. [Effects of the Invention]

[0007] The present invention provides a novel antiviral agent. [Brief explanation of the drawings]

[0008] [Figure 1] 1 is a graph showing the viral genome amount in an inhibition test. [Figure 2] 1 is a graph showing the viral genome amount in an inhibition test. [Figure 3] 1 is a graph showing relative fluorescence intensity in an inhibition test. DETAILED DESCRIPTION OF THE INVENTION

[0009] Hereinafter, the embodiments for carrying out the present invention will be described in detail, but the present invention is not limited to the following embodiments. In this specification, the term "comprise" encompasses the meanings of "essentially consist of" and "consist of only."

[0010] The antiviral agent of the present invention contains, as an active ingredient, at least one selected from the group consisting of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin, or propolis derived from the genus Macaranga. Hereinafter, in this specification, the components selected from the group consisting of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin, and propolis derived from the genus Macaranga, may be collectively referred to as the "active ingredient." In this specification, "propolis derived from the genus Macaranga" is synonymous with "propolis derived from the genus Macaranga."

[0011] Viruses that can be treated with antiviral agents include, for example, RNA viruses such as single-stranded positive-strand RNA viruses and single-stranded negative-strand RNA viruses, DNA viruses such as DNA viruses with linear double-stranded DNA, and enveloped or non-enveloped viruses. Specific examples of viruses include SARS-CoV-2 (novel coronavirus), norovirus, feline calicivirus, and other viruses belonging to the Caliciviridae family, influenza virus, Sendai virus, and vaccinia virus.

[0012] The active ingredient has excellent antiviral activity. The antiviral agent according to this embodiment contains the active ingredient, and therefore has excellent antiviral activity. "Antiviral" may mean, for example, inactivating viruses, inhibiting viral replication, inhibiting viral adsorption and entry into cells, or inhibiting viral budding from cells. The antiviral agent according to this embodiment can be used to prevent and / or ameliorate viral infections.

[0013] The antiviral agent according to this embodiment may contain at least one active ingredient selected from the group consisting of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin. Nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin are all components that have been confirmed to be present in propolis derived from the Macaranga genus. These components are also known to be present in the Macaranga plant itself.

[0014] Nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin used as active ingredients in the antiviral agent of this embodiment may be naturally derived, such as from propolis derived from the genus Macaranga, or from Macaranga plants, or may be synthetic products. Macaranga plants may be, for example, fruits, seeds, flowers, roots, trunks, stems, leaves, etc. of Macaranga. Macaranga species may include, for example, Macaranga tanarius, Macaranga alnifolia, Macaranga pruinosa, and Macaranga triloba.

[0015] The antiviral agent of this embodiment contains at least one active ingredient selected from the group consisting of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin, and preferably contains nymphaeol A, nymphaeol B, nymphaeol C, and isonymphaeol B. It may contain all of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin. When the antiviral agent of this embodiment contains at least one active ingredient selected from the group consisting of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin, these components may be contained in the antiviral agent as propolis derived from the genus Macaranga or as a Macaranga plant.

[0016] The content of each of the components nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin in the antiviral agent according to this embodiment, and the total content of these components, are not particularly limited as long as the effects of the present invention can be obtained, and can be appropriately adjusted depending on the final form, etc., and can be, for example, 0.00001% by mass or more, 0.0001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more, or more, based on the total solid content in the antiviral agent. % or more, 7% by mass or more, 10% by mass or more, 15% by mass or more, 20% by mass or more, 30% by mass or more, 40% by mass or more, 50% by mass or more, 60% by mass or more, 70% by mass or more, 80% by mass or more, or 90% by mass or more, and 100% by mass or less, 90% by mass or less, 80% by mass % or less, 70 mass% or less, 60 mass% or less, 55 mass% or less, 50 mass% or less, 40 mass% or less, 30 mass% or less, 20 mass% or less, 15 mass% or less, 10 mass% or less, 7 mass% or less, 5 mass% or less, 3 mass% or less, 1 mass% or less, or 0.5 mass% or less.

[0017] The antiviral agent according to this embodiment may contain propolis, derived from the genus Macaranga, as an active ingredient. Propolis is a resinous or waxy substance that forms the walls of beehives and is made by mixing plant buds or resins collected by bees with their saliva. Propolis can be obtained, for example, as a beekeeping product according to conventional methods.

[0018] The propolis used in the antiviral agent according to this embodiment is not particularly limited as long as it is derived from the genus Macaranga, and may be derived from any place of origin, such as Japan (Okinawa), China, Taiwan, Malaysia, Oceania, or Hawaii.

[0019] Propolis is characterized by the flavonoids and other components it contains, depending on the plant it comes from. Propolis from the Macaranga genus is characterized by containing at least one compound selected from the group consisting of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin.

[0020] Examples of propolis originating from the Macaranga genus include Macaranga (Macaranga tanarius), Macaranga alnifolia, Macaranga pruinosa, and Macaranga triloba. Propolis originating from the Macaranga genus is preferably Macaranga (Macaranga tanarius). Propolis originating from the Macaranga genus is characterized by the inclusion of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin. Meanwhile, propolis originating from plants other than the Macaranga genus has not been found to contain nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin. For example, Brazilian green propolis does not contain any of these five components.

[0021] Propolis derived from Macaranga may contain about 0-26% by mass of nymphaeol A, about 0-20% by mass of nymphaeol B, about 14-40% by mass of nymphaeol C, about 0-12% by mass of isonymphaeol B, and about 0-9% by mass of 3'-geranylnaringenin in the extracted solids. In particular, propolis derived from Macaranga may contain about 22-26% by mass of nymphaeol A, about 17-20% by mass of nymphaeol B, about 14-16% by mass of nymphaeol C, about 5-12% by mass of isonymphaeol B, and about 4-9% by mass of 3'-geranylnaringenin in the extracted solids. The antiviral agent according to this embodiment may contain nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin in the above ratios.

[0022] The propolis derived from the genus Macaranga and used as the active ingredient of the antiviral agent of this embodiment may be, for example, raw propolis or a processed propolis product obtained by subjecting raw propolis to some processing. The processed propolis product may be, for example, raw propolis that has been subjected to processing such as pulverization, extraction, concentrated or powdered extract, or granulated powder, or may be the extraction residue remaining after extraction. That is, the processed propolis product may be, for example, a pulverized propolis product, an extract, a concentrated extract, an extract powder, an extract granules, or an extraction residue. The extraction may be, for example, water extraction, hydrophilic organic solvent extraction, or supercritical extraction. Examples of hydrophilic organic solvents include ethanol, glycerin, and 1,3-butylene glycol. The propolis extract may be obtained by extraction from raw propolis or by further extraction from the extraction residue. A single processing method may be used, or two or more methods may be combined. As the processed propolis product, a propolis hydrophilic organic solvent extract is preferred because it allows the active ingredients of propolis to be extracted efficiently and in a balanced manner in a short time. The processed propolis product is preferably a propolis ethanol extract.

[0023] The propolis extract includes the recovered extract (including further purified extracts as necessary), concentrates obtained by concentrating the extract, and solids obtained by removing the solvent from the extract by freeze-drying, spray-drying, etc. The concentration, freeze-drying, and spray-drying of the extract can be carried out according to conventional methods. The propolis extract may be in the form of a powder obtained by powdering the extract, or a granule obtained by granulating the powder.

[0024] The content of propolis originating from the genus Macaranga in the antiviral agent according to this embodiment is not particularly limited as long as it is within a range in which the effects of the present invention can be obtained, and can be appropriately adjusted depending on the final form, etc., and may be, for example, 0.00001% by mass or more, 0.0001% by mass or more, 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, 3% by mass or more, 5% by mass or more, 7% by mass or more, 10% by mass or more, 15% by mass or more relative to the total amount of solids in the antiviral agent. , 20% by mass or more, 30% by mass or more, 40% by mass or more, 50% by mass or more, 60% by mass or more, 70% by mass or more, 80% by mass or more, or 90% by mass or more, and 100% by mass or less, 90% by mass or less, 80% by mass or less, 70% by mass or less, 6 It may be 0 mass% or less, 55 mass% or less, 50 mass% or less, 40 mass% or less, 30 mass% or less, 20 mass% or less, 15 mass% or less, 10 mass% or less, 7 mass% or less, 5 mass% or less, 3 mass% or less, 1 mass% or less, or 0.5 mass% or less.

[0025] The antiviral agent according to this embodiment can also be administered to humans, for example, for use in the treatment and / or prevention of viral infections. The antiviral agent according to this embodiment can be administered orally or parenterally. Oral administration can be enteral administration. Parenteral administration can be topical administration, particularly transdermal administration.

[0026] The dosage of the antiviral agent according to this embodiment when administered orally may vary depending on the form of the active ingredient and the application method and amount, but may be, for example, 1 μg to 1,000 mg, 2 μg to 500 mg, 3 μg to 250 mg, or 4 μg to 100 mg of the active ingredient or antiviral agent per day, calculated on a dry solids basis, for an adult weighing 60 kg. The dosage can be increased or decreased as appropriate depending on factors such as the health condition of the person taking the agent, the administration method, the type of active ingredient, and the combination with other agents.

[0027] The antiviral agent according to this embodiment may be administered once a day, or in divided doses such as twice or three times a day, as long as the effective daily dose is within the above-mentioned range. The antiviral agent according to this embodiment is effective immediately after administration, but continuous administration for 1 to 4 weeks, or for one month or more, six months or more, or one year or more is preferred because the effect can be sustained longer.

[0028] The dosage of the antiviral agent according to this embodiment when administered parenterally may vary depending on the active ingredient, the site of application, and the range of application. For example, the amount of the active ingredient or antiviral agent to be applied to the skin may be 1 mg to 1000 mg, 1.5 mg to 900 mg, 1.8 mg to 800 mg, or 2 mg to 700 mg in terms of dry solid content.

[0029] The antiviral agent according to this embodiment can be used as a food composition (particularly a food composition intended for health, health maintenance, or health promotion (e.g., health food, functional food, nutritional composition, dietary supplement, supplement, health food, food for specified health uses, nutrient functional food, or food with functional claims)), cosmetic, disinfectant, cleaning agent, quasi-drug, pharmaceutical, etc.

[0030] The antiviral agent according to this embodiment may be an additive that imparts an antiviral effect.

[0031] The antiviral agent according to this embodiment can be used as a food composition, cosmetic, disinfectant, cleaning agent, quasi-drug, or pharmaceutical product itself, or can also be used as an ingredient in a food composition, cosmetic, disinfectant, cleaning agent, quasi-drug, or pharmaceutical product. A food composition, cosmetic, disinfectant, cleaning agent, quasi-drug, or pharmaceutical product containing the antiviral agent according to this embodiment as an ingredient can be produced, for example, by adding the antiviral agent according to this embodiment to an intermediate product in the production process of these products.

[0032] The food composition may also contain minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, colorants, flavorings, stabilizers, gelling agents, preservatives, sustained-release regulators, surfactants, solubilizers, humectants, etc., as needed.

[0033] Food compositions include any food or beverage that can be ingested by animals (including humans). The types of food compositions are not particularly limited, and examples include dairy products; fermented foods (yogurt, etc.); beverages (soft drinks such as coffee, juice, and tea drinks, dairy drinks, lactic acid bacteria drinks, lactic acid bacteria-containing drinks, yogurt drinks, carbonated drinks, sake, Western liquor, and alcoholic beverages such as fruit wine); spreads (custard cream, etc.); pastes (fruit paste, etc.); Western confectionery (chocolate, donuts, pies, cream puffs, gum, gummy candies, jellies, candies, cookies, cakes, puddings, etc.); Japanese confectionery (daifuku, mochi, manju, castella, anmitsu, yokan, etc.); frozen desserts (ice cream, popsicles, sorbets, etc.); foods (curry, beef bowls, rice porridge, miso soup, soup, meat sauce, pasta, pickles, jam, etc.); and seasonings (dressings, furikake, umami seasonings, soup bases, etc.).

[0034] The method for producing the food composition is not particularly limited, and any known method can be used as appropriate.

[0035] The dosage unit form when used as a supplement is not particularly limited and can be selected appropriately. Examples of the form of the supplement include chewable tablets, troches, capsules, granules, liquids, powders, syrups, pastes, drinks, gummies, etc.

[0036] In addition to the above-mentioned active ingredients, the cosmetic product may contain ingredients commonly used in cosmetics, such as disinfectants, preservatives, surfactants, alcohols, aqueous components, water, colorants, pH adjusters, solubilizers, abrasives, foaming agents, enzymes, flavoring agents, chelating agents, excipients, thickeners, bases, emulsifiers, solvents, stabilizers, oils, cleaning agents (lactic acid bacteria), whitening agents, moisturizers, antioxidants, UV absorbers, powder components, coloring materials, and various skin nutrients, as needed.

[0037] Cosmetic raw materials may be in any form, such as solid, liquid, or paste. Cosmetics may be medicated cosmetics (i.e., quasi-drugs). Cosmetics include all cosmetics that can be applied to the skin, mucous membranes, body hair, head hair, scalp, nails, teeth, facial skin, lips, and other areas of animals (including humans).

[0038] Cosmetics can take a wide range of formulations, including aqueous solutions, solubilized solutions, emulsions, powders, oils, gels, ointments, aerosols, two-layer water-oil systems, and three-layer water-oil-powder systems.

[0039] The disinfectant or cleaner contains an effective amount of the active ingredient and has the effect of eliminating, reducing, or killing viruses. The disinfectant or cleaner may be in any form, such as a solid, liquid, or paste. The disinfectant or cleaner is preferably, for example, a wet tissue-like disinfecting sheet or cleaning sheet, a spray, or a paste, or may be, for example, a diluted solution of the active ingredient using water, hydroalcohol, alcohol, or the like as a solvent.

[0040] The effective amount of the active ingredient in the disinfectant or cleaner is not particularly limited, and may be 0.1% by weight to 100% by weight, or may be 1% by weight to 90% by weight, 10% by weight to 80% by weight, or 25% by weight to 50% by weight. The method for producing the disinfectant or cleaner is not particularly limited, and can be any known method as appropriate.

[0041] The above active ingredients may be used alone in pharmaceutical preparations, or may be mixed with other medicinal ingredients such as vitamins and herbal medicines listed in the Japanese Pharmacopoeia.

[0042] When the antiviral agent according to this embodiment is prepared as a pharmaceutical, the active ingredient can be prepared, together with pharmaceutical acceptable ingredients, into the form of a tablet (including plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsule, pill, powder (powder), fine granules, granules, liquid, suspension, emulsion, syrup, paste, injection (including the case where the agent is mixed with distilled water or an infusion such as an amino acid infusion or an electrolyte infusion at the time of use to prepare a liquid), or the like, to form a pharmaceutical preparation.

[0043] Pharmaceuticals may be administered locally or systemically. There are no particular limitations on the administration method, and they may be administered orally or parenterally. Parenteral administration routes include subcutaneous, intradermal, intramuscular, intraperitoneal, intravenous or intraarterial administration, and transdermal administration.

[0044] In addition to the above-mentioned active ingredient, the pharmaceutical product according to this embodiment may contain, as needed, pharmaceutically acceptable ingredients such as excipients, binders, disintegrants, lubricants, colorants, suspending agents, thickeners, antioxidants, absorption enhancers, pH adjusters, preservatives, antiseptics, stabilizers, surfactants, sweeteners, flavoring agents, and fragrances.

[0045] The antiviral agent according to the present embodiment described above can be applied to mammals including humans (preferably humans).

[0046] The antiviral agent according to this embodiment uses propolis, which has been used as a food material in the past, or naturally occurring components as active ingredients, and is therefore highly safe. [Example]

[0047] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to the following examples.

[0048] [Test sample preparation method] (Propolis derived from Macaroni tanarius) 80% ethanol by volume was added to the ground raw mass of Macaroni-derived propolis, and the mixture was stirred and extracted at room temperature for 1 hour. After extraction, filtration was performed to obtain a first extract and a residue. 80% ethanol by volume was added to the residue again, and the mixture was stirred and extracted in the same manner to obtain a second extract. The first and second extracts were mixed, filtered through filter paper (No. 2, manufactured by Advantec Toyo Co., Ltd.), and then concentrated under reduced pressure using an evaporator. The concentrated liquid was freeze-dried to obtain Macaroni-derived propolis extract.

[0049] (Prenylflavonoids) Nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin were all purchased from NatuPharma Ryukyu Co., Ltd. (derived from Macaranga tanarius fruit) and used.

[0050] (Echinacea extract powder) Water was added to dried aerial parts of Echinacea (including leaves, stems, and flowers), mixed, and extracted with hot water at 90°C for 1 hour. After extraction, the mixture was filtered to obtain a first extract and a residue. The residue was further extracted with hot water at 90°C for 30 minutes and filtered to obtain a second extract. The first and second extracts were mixed and concentrated under reduced pressure. An excipient was then added to the mixture to make up 10% of the solid content, and the mixture was spray-dried to obtain a powder, which was used as a sample.

[0051] (Remdesivir) Remdesivir (GS-5734) from Selleckchem was used.

[0052] The viruses used were SARS-CoV-2 (D614G-GFP strain), influenza virus (A / Udorn / 72 (H3N2)), feline calicivirus (F9 strain), Sendai virus (Z strain), and vaccinia virus (WR strain). Since norovirus propagation methods have been established, feline calicivirus, which belongs to the same Caliciviridae family, is generally used instead to evaluate its efficacy.

[0053] [Inhibition test] Each test sample was dissolved in water or DMSO and serially diluted with serum-free DMEM. 50 ul of each serially diluted solution was added to each virus solution (4E+3 TCID in the case of MOI=0.01). 50 / ml, 2E+6 TCID at MOI=5 50 The test samples were mixed in equal amounts (10,000 cells / ml) and incubated at 37°C for 1 hour. Then, 50 μl of each test sample-virus mixture was inoculated into TMPRSS2-expressing Vero cells (10,000 cells / well) seeded in a 96-well plate and incubated at 37°C for 2 hours. After incubation, the inoculum was removed from each well, washed three times with serum-free DMEM, and then serum-free DMEM was added to each test sample to the same final concentration as the test sample-virus mixture. The plate was then incubated at 37°C for 48 hours.

[0054] For each virus, 10 μl of culture supernatant was collected 24 hours and 48 hours after infection, and the viral genome amount in the supernatant was quantified by qRT-PCR to calculate the IC50.

[0055] In the inhibition test, the test sample and virus are mixed before cell culture, and the mixture is inoculated onto the cells, and the maintenance medium after inoculation also contains the test sample. Therefore, the amount of budded virus (measured by PCR) in this test is thought to be affected by at least one of the following: a direct agglutination or disruption effect of the test sample on the virus, an inhibitory effect on the absorption and penetration of the virus into the cells, and an inhibitory effect on the replication of the virus within the cells.

[0056] The IC50 of each test sample against SARS-CoV-2 in the inhibition test is shown in Table 1.

[0057] [Table 1]

[0058] Macaroni-derived propolis had a significantly lower IC50 against the SARS-CoV-2 virus in an inhibition test compared to echinacea. Furthermore, five components—nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin—also showed lower IC50s against the SARS-CoV-2 virus compared to echinacea and remdesivir. These results suggest that Macaroni-derived propolis, nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin may have aggregating or disrupting effects on viruses, as well as inhibitory effects on viral uptake and entry into cells.

[0059] The evaluation results of Macaroni tanarius-derived propolis against feline calicivirus and influenza virus in the inhibition test are shown in Figure 1. Macaroni tanarius-derived propolis was shown to have antiviral effects against feline calicivirus and influenza virus.

[0060] Inhibition tests were conducted in the same manner as above, using vaccinia virus and Sendai virus as the viruses and Macaroni tanarius-derived propolis (10 μg / ml) as the test sample. The amount of viral genome in the supernatant is shown in Figure 2. PP in the figure indicates Macaroni tanarius-derived propolis. Macaroni tanarius-derived propolis was shown to have antiviral effects against both vaccinia virus and Sendai virus.

[0061] Inhibition tests were performed using recombinant Sendai virus expressing GFP and Macaroni propolis (PP, 10 μg / mL), nymphaeol A (NA, 2.7 μg / mL), nymphaeol B (NB, 2.5 μg / mL), nymphaeol C (NC, 3.0 μg / mL), isonymphaeol B (iN-B, 3.0 μg / mL), and 3'-geranylnaringenin (3GN, 2.5 μg / mL) as test samples. Cells were observed at 24 and 48 hours after infection using a Keyence all-in-one fluorescence microscope BZ-X810, and GFP fluorescence intensity was quantified. The results are shown in Figure 3.

[0062] The fluorescence intensity measurement reflects the combined intracellular and extracellular viral load. When Macaroni-derived propolis, nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, or 3'-geranylnaringenin was used, the relative fluorescence intensity was significantly lower than that of the control, or no fluorescence was observed at all. Macaroni-derived propolis, nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin were shown to have antiviral effects against Sendai virus.

Claims

1. An antiviral agent comprising, as an active ingredient, at least one member selected from the group consisting of nymphaeol A, nymphaeol B, nymphaeol C, isonymphaeol B, and 3'-geranylnaringenin.

2. An antiviral agent containing propolis, derived from the Macaranga genus of plants, as an active ingredient.

3. The antiviral agent according to claim 1 or 2 against SARS-CoV-2.

4. 3. The antiviral agent according to claim 1 or 2, which is effective against at least one virus selected from the group consisting of influenza virus, viruses belonging to the Caliciviridae family, Sendai virus, and vaccinia virus.

5. The antiviral agent according to claim 1 or 2, which is a food composition, a cosmetic, a disinfectant, a cleaning agent, or a quasi-drug.

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