Virus cell entry inhibitor

Abstract

The present invention addresses the problem of providing a virus cell entry inhibitor that inhibits the entry of viruses into cells and makes it possible to prevent viral infections.　A virus cell entry inhibitor that solves the problem of the present invention is characterized by containing at least one selected from an eyebright extract, a kasoori methi extract, a Tartary buckwheat extract, an okra extract, a cinnamon extract, a berberry extract, and a shell ginger extract.

Description

Virus cell entry inhibitor

[0001] The present invention relates to a virus cell entry inhibitor.

[0002] Viral infectious diseases are diseases that cause severe symptoms such as cold symptoms, pneumonia, hepatitis, encephalitis, etc., and infect not only humans but also animals such as birds and dogs. In recent years, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has run rampant around the world, affecting not only lives and health but also economic activities and social functions.

[0003] Viruses, which are the cause of viral infectious diseases, do not have the ability to self-proliferate. They bind to receptors on the surface of host cells and adsorb, then penetrate into the cells and proliferate. Therefore, it is considered effective to inhibit the entry of viruses into host cells as a prevention of viral infectious diseases.

[0004] For example, Patent Document 1 discloses that silver-bonded fucoidan in which silver is bonded to the sulfate group of fucoidan derived from brown algae inhibits the binding of receptors on the cell surface to viruses and has an antiviral effect.

[0005] International Publication No. 2023 / 243525

[0006] The present invention provides a virus cell entry inhibitor that inhibits the entry of viruses into cells and enables the prevention of viral infectious diseases.

[0007] As a result of intensive studies to solve the above problems, the present inventors have found that an extract obtained from a specific plant inhibits the entry of viruses into cells and can prevent viral infectious diseases, thus completing the present invention.

[0008] The present invention includes the following embodiments: [1] A viral cell entry inhibitor comprising at least one selected from eyebright extract, fenugreek extract, buckwheat extract, okra extract, cinnamon extract, barberry extract, and ginger lily extract. [2] The viral cell entry inhibitor according to [1], wherein the virus is SARS-CoV-2. [3] An influenza virus cell entry inhibitor comprising at least one selected from eyebright extract, fenugreek extract, buckwheat extract, okra extract, cinnamon extract, and ginger lily extract. [4] The influenza virus cell entry inhibitor according to [3], wherein the influenza virus is the H5N1 subtype influenza virus. [5] The viral cell entry inhibitor according to any one of [1] to [4], which is a food, supplement, or animal feed. [6] The viral cell entry inhibitor according to any one of [1] to [4], which is a pharmaceutical product.

[0009] The viral cell entry inhibitor of the present invention has excellent ability to inhibit viral cell entry and can therefore prevent viral infections.

[0010] Figure 1 shows the results of measuring the cell entry inhibitory activity of SARS-CoV-2 by cell entry inhibitors for each virus (bar graph) and the results of cell survival assays (line graph). The bar graph shows the luciferase emission intensity of the group to which each virus's cell entry inhibitor was added compared to the control group without the addition of each virus's cell entry inhibitor. The line graph shows the absorbance at 490 nm of the group to which each virus's cell entry inhibitor was added compared to the absorbance at 490 nm of the control group without the addition of each virus's cell entry inhibitor. Figure 2 shows the results of measuring the cell entry inhibitory activity of influenza virus by cell entry inhibitors for each virus. The bar graph shows the luciferase emission intensity of the group to which each virus's cell entry inhibitor was added compared to the luciferase emission intensity of the control group without the addition of each virus's cell entry inhibitor.

[0011] The details of the present invention will be described below. The description of the present invention below may be based on preferred embodiments of the present invention, but the present invention is not limited to such embodiments. In this specification, the "~" indicating a numerical range is used to mean that the numbers before and after it are included as the lower limit and upper limit.

[0012] The virus cell entry inhibitor of the present invention comprises at least one selected from eyebright extract, fenugreek extract, buckwheat extract, okra extract, cinnamon extract, barberry extract, and ginger lily extract.

[0013] (Eyebright) Eyebright (Euphrasia officinalis), the raw material for eyebright extract, is an annual herbaceous plant belonging to the genus Euphrasia in the family Scrophulariaceae. It is native to Europe and is also distributed in West Asia and North America. It has long been known to have effects that improve eye strain and eye diseases such as conjunctivitis.

[0014] In this invention, there are no particular restrictions on the origin or type of eyebright; any origin or type can be used. Furthermore, there are no particular restrictions on the part of the eyebright used; for example, one or more parts such as the whole plant, roots, stems, leaves, flowers, or seeds can be used. Among these, the use of leaves is preferred.

[0015] When obtaining eyebright extract, the raw material eyebright may be fresh or dried. Furthermore, crushed or pulverized material obtained by crushing or pulverizing fresh or dried material according to conventional methods may be used. Among these, from the viewpoint of extraction efficiency, it is preferable to use dried crushed or dried pulverized eyebright, and more preferable to use dried pulverized eyebright.

[0016] (Kasuri Methi) Kasuri methi, the raw material for kasuri methi extract, is the dried leaves of fenugreek (Trigonella foenum-graecum), an annual plant belonging to the Fabaceae Trigonella genus. It is also known as "fenugreek leaf." Native to the Mediterranean region, it is cultivated in the Middle East, Africa, and India. The seeds and leaves are used as a spice in curries and other dishes. It is known to have antiglycemia-lowering and anti-inflammatory effects.

[0017] In this invention, there are no particular restrictions on the origin or type of fenugreek used as the raw material for kasuri methi, and any origin or type can be used. When obtaining kasuri methi extract, from the viewpoint of extraction efficiency, it is preferable to use crushed or pulverized kasuri methi, and more preferably to use pulverized kasuri methi.

[0018] (Tartary buckwheat) Tartary buckwheat (Fagopyrum tataricum), the raw material for Tartary buckwheat extract, is an annual plant belonging to the Polygonaceae family, genus Fagopyrum, and is cultivated in China, Japan, Russia, Nepal, EU countries, etc. Tartary buckwheat contains about 100 times more rutin, a type of polyphenol, than other varieties of buckwheat, and is attracting attention as a health food. The rutin contained in Tartary buckwheat is broken down by the rutin-degrading enzyme rutinosidase when water is added, producing the bitter component quercetin. For this reason, Tartary buckwheat is also known as "bitter buckwheat."

[0019] In this invention, there are no particular restrictions on the origin or type of Tartary buckwheat used as the raw material for the Tartary buckwheat extract; any origin or type can be used. Furthermore, there are no particular restrictions on the part of the Tartary buckwheat used; for example, one or more parts such as the whole plant, roots, stems, leaves, flowers, and seeds can be used. Among these, the use of seeds is preferred.

[0020] When obtaining Tartary buckwheat extract, fresh or dried Tartary buckwheat may be used as the raw material. Furthermore, crushed or pulverized material obtained by crushing or pulverizing fresh or dried material according to conventional methods may be used. Among these, from the viewpoint of extract efficiency, it is preferable to use dried crushed or dried pulverized Tartary buckwheat, and more preferable to use dried pulverized Tartary buckwheat.

[0021] (Okra) Okra (Abelmoschus esculentus), the raw material for okra extract, is a perennial plant belonging to the Malvaceae family, genus Abelmoschus. However, in temperate regions including Japan, it cannot survive the winter and is therefore cultivated as an annual plant. It is native to northeastern Africa and is mainly cultivated in Africa, South Asia, and other areas. Okra fruit is rich in water-soluble dietary fiber pectin, arapin, galactan, etc., and is known to have cholesterol absorption inhibitory effects.

[0022] In this invention, there are no particular restrictions on the origin or type of okra used as the raw material for the okra extract; okra from any origin or type can be used. Furthermore, there are no particular restrictions on the part of the okra used; for example, one or more parts such as the whole plant, roots, stems, leaves, flowers, fruits, and seeds can be used. Among these, the use of the fruit is preferred.

[0023] When obtaining okra extract, fresh or dried okra may be used as the raw material. Furthermore, crushed or pulverized material obtained by crushing or pulverizing fresh or dried okra according to conventional methods may also be used. Among these, from the viewpoint of extract efficiency, it is preferable to use dried crushed or dried pulverized okra, and more preferably to use dried pulverized okra.

[0024] (Cinnamon) Cinnamon, the raw material for cinnamon extract, is the dried bark of Cinnamomum cassia (Tonkin cinnamon) and other related plants of the Lauraceae family, and is distributed in southwestern China, Vietnam, and other areas. Cinnamon contains 1-2% essential oil, cinnamaldehyde, eugenol, safrole, phellandrene, linalool, and other components, and is known to have stomachic, diaphoretic, antipyretic, and analgesic effects.

[0025] In the present invention, there are no particular restrictions on the origin or type of cinnamon used as the raw material for the cinnamon extract; any origin or type can be used. When obtaining the cinnamon extract, cinnamon may be used as is, or crushed or pulverized cinnamon may be used after crushing or pulverizing it according to conventional methods. In particular, from the viewpoint of extract efficiency, it is preferable to use dried crushed or dried pulverized cinnamon, and it is more preferable to use dried pulverized cinnamon.

[0026] (Barberry) Barberry, the raw material for barberry extract, is a deciduous shrub belonging to the genus Berberis in the family Berberidaceae, and is widely distributed in Asia, South America, Africa, and Europe. Barberry contains berberine, a type of benzylisoquinoline alkaloid, or its salts (e.g., hydrochloric acid, sulfuric acid, etc.), which is known to have a bactericidal effect against harmful bacteria in the intestines.

[0027] In this invention, there are no particular restrictions on the origin or type of barberry used as the raw material for the barberry extract; barberry from any origin or type can be used. Furthermore, there are no particular restrictions on the part of the barberry used; for example, one or more parts such as the whole plant, roots, stems, leaves, bark, flowers, fruits, and seeds can be used. Among these, the use of roots and bark is preferred.

[0028] When obtaining barberry extract, the raw material may be fresh barberries or dried barberries. Furthermore, crushed or pulverized barberries obtained by crushing or pulverizing fresh or dried barberries according to conventional methods may also be used. Among these, from the viewpoint of extract efficiency, it is preferable to use dried crushed or dried pulverized barberries, and more preferable to use dried pulverized barberries.

[0029] (Getto) Getto (Alpinia zerumbet), the raw material for Getto extract, is a perennial evergreen plant belonging to the genus Alpinia in the family Zingiberaceae, and is distributed in Southeast Asia, Taiwan, Okinawa, and the Ogasawara Islands. In Okinawa, it is called "sannin" and is used in the local dish "mochi". Getto contains components such as citral and limonene, and is known to have antibacterial and insecticidal properties.

[0030] In this invention, there are no particular restrictions on the origin or type of Alpinia zerumbet used as the raw material for the Alpinia zerumbet extract; any origin or type can be used. Furthermore, there are no particular restrictions on the part of the Alpinia zerumbet used; for example, one or more parts such as the whole plant, roots, stems, leaves, flowers, and seeds can be used. Among these, the use of leaves and stems is preferred.

[0031] When obtaining Alpinia zerumbet extract, either fresh or dried Alpinia zerumbet plants may be used as the raw material. Furthermore, crushed or pulverized materials obtained by crushing or pulverizing fresh or dried plants according to conventional methods may also be used. Among these, from the viewpoint of extract efficiency, it is preferable to use dried crushed or dried pulverized Alpinia zerumbet, and more preferable to use dried pulverized Alpinia zerumbet.

[0032] The method for obtaining the extract from the above raw materials is not particularly limited, and known methods for producing plant extracts can be used. Specifically, for example, the extract can be produced by drying, crushing, or grinding each raw material as necessary, adding an extraction solvent, and then heating it at room temperature or under heating conditions, but it is particularly preferable to produce the extract under heating conditions.

[0033] The extraction solvent is not particularly limited, and examples include aqueous solvents such as water, physiological saline, phosphate buffer, and borate buffer; alcohols such as methanol, ethanol, propylene glycol, and 1,3-butylene glycol; ketones such as acetone and methyl ethyl ketone; esters such as methyl acetate and ethyl acetate; linear and cyclic ethers such as tetrahydrofuran and diethyl ether; halogenated hydrocarbons such as dichloromethane, chloroform, and carbon tetrachloride; hydrocarbons such as hexane, cyclohexane, and petroleum ether; and aromatic hydrocarbons such as benzene and toluene. One or more of these can be used. As stated above, the extraction solvent of the present invention is not particularly limited, but it is preferable to use water, especially hot water.

[0034] The extraction conditions, such as the amount of extraction solvent, extraction time, and extraction temperature, are not particularly limited and can be appropriately selected according to the characteristics of each raw material. For example, the amount of extraction solvent is 10 to 40 parts by weight, preferably 20 to 25 parts by weight, per 1 part by weight of the dry weight of the raw material. For example, the extraction temperature is 80 to 100°C, preferably 95 to 100°C. For example, the extraction time is 0.25 to 2 hours, preferably 0.5 to 1 hour.

[0035] After extraction, the obtained extract may be used as is, or it may be purified by known methods as needed. Examples of purification methods include solid-liquid separation by filtration, centrifugation, etc.; concentration by evaporation, membrane concentration, etc.; drying by hot air drying, vacuum drying, freeze-drying, etc., and these may be combined.

[0036] The virus cell entry inhibitor of the present invention, which contains the above extract, is not particularly limited to any virus, and may be either a DNA virus or an RNA virus. However, it is preferably used for RNA viruses such as norovirus, enterovirus, coronavirus, influenza virus, rubella virus, Japanese encephalitis virus, dengue virus, and Ebola virus, and is more preferably used for coronaviruses and influenza viruses.

[0037] Examples of coronaviruses include human coronaviruses such as HCoV-NL63, HCoV-OC43, HCoV-HKU1, and HCoV-229E; severe acute respiratory syndrome coronaviruses such as SARS-CoV and SARS-CoV-2; and Middle East respiratory syndrome coronaviruses. Of these, severe acute respiratory syndrome coronaviruses such as SARS-CoV and SARS-CoV-2 are preferred, and SARS-CoV-2 is more preferred, from the viewpoint of easily obtaining the effects of the present invention.

[0038] Examples of influenza viruses include type A influenza viruses such as H1N1, H3N2, H5N1, and H7N9 subtypes; type B influenza viruses such as Yamagata and Victoria lineages; and type C influenza viruses. Of these, type A influenza viruses such as H1N1, H3N2, H5N1, and H7N9 subtypes are preferred from the viewpoint of easily obtaining the effects of the present invention, and the H5N1 subtype is particularly preferred.

[0039] The mechanism by which the viral cell entry inhibitor of the present invention inhibits viral entry into cells is not clear, but it is presumed to be as follows: Viral cell entry occurs when membrane proteins on the surface of the virus bind to receptors on the host cell and form membrane fusion. It is presumed that the plant extract contained in the viral cell entry inhibitor of the present invention inhibits viral entry into cells by binding to viral membrane proteins or covering the surface of the virus.

[0040] The concentration of each plant extract contained in the viral cell entry inhibitor of the present invention can be appropriately selected depending on the type of virus, for example, 0.1 to 300 μg / ml, preferably 3 to 150 μg / ml. For example, when using the viral cell entry inhibitor of the present invention against SARS-CoV-2, the concentrations of eyebright extract, fenugreek extract, cinnamon extract, and ginger lily extract are not particularly limited, but are preferably 0.5 to 300 μg / ml, more preferably 5 to 200 μg / ml, and even more preferably 50 to 150 μg / ml. The concentrations of buckwheat extract and okra extract are not particularly limited, but are preferably 5 to 300 μg / ml, more preferably 15 to 200 μg / ml, and even more preferably 50 to 150 μg / ml. The concentration of the barberry extract is not particularly limited, but is preferably 0.5 to 300 μg / ml, more preferably 15 to 200 μg / ml, and even more preferably 50 to 150 μg / ml.

[0041] The viral cell entry inhibitor of the present invention can be formulated in combination with the above extract, and optionally with a pharmaceutically acceptable carrier, and used as a pharmaceutical. Pharmaceuticals include throat sprays and lozenges, etc. Examples of pharmaceutically acceptable carriers include glucose, lactose, starch, mannitol, dextrin, fatty acid glycerides, polyethylene glycol, hydroxyethyl starch, ethylene glycol, polyoxyethylene sorbitan fatty acid esters, amino acids, gelatin, albumin, water, physiological saline, etc. Furthermore, conventional additives such as stabilizers, wetting agents, emulsifiers, binders, isotonic agents, and excipients can be added as needed. The dosage form is not particularly limited, but examples include liquids, powders, granules, capsules, tablets, etc., and can be manufactured according to conventional methods.

[0042] The viral cell entry inhibitor of the present invention can also be in the form of food or drink. Known food additives and / or food materials are blended with the above extract and prepared according to a conventional method. Its form is not particularly limited, and examples include various supplements, bread, biscuits, hot cakes, noodles, starch-based foods such as tablets, gums, candies, Japanese confectioneries, livestock foods such as ham and sausage, fish and meat foods such as chikuwa and kamaboko, seafood foods, seasonings such as dressings, soy sauce, jam, and furikake, beverages such as tea, juice, soft drinks, and alcoholic beverages, etc.

[0043] The viral cell entry inhibitor of the present invention can also be in the form of feed or pet food. Known feed materials, gelling agents, shape retainers, pH adjusters, seasonings, preservatives, nutritional enhancers, etc. are appropriately blended with the above extract and prepared according to a conventional method. Its form is not particularly limited, and any form such as pellet, flake, mash, etc. can be exemplified. For example, it can be used as feed for livestock such as cows, pigs, chickens, sheep, horses, and pet food for dogs, cats, etc. Furthermore, as described above, since the viral cell entry inhibitor of the present invention binds to the virus or covers the surface of the virus, it is also applicable to sprays and nasal washes used for masks, etc.

[0044] The influenza virus cell entry inhibitor of the present invention contains at least one selected from an eyebright extract, a kosamet extract, a tartary buckwheat extract, an okra extract, a cinnamon extract, and a shell ginger extract. In the influenza virus cell entry inhibitor of the present invention, parts similar to the composition of the above viral cell entry inhibitor are appropriately omitted from the description.

[0045] The influenza virus targeted by the influenza virus cell entry inhibitor of the present invention includes, for example, the above-mentioned influenza viruses. Among them, it is preferably used for the H5N1 subtype influenza virus. The H5N1 subtype influenza virus is a type of highly pathogenic avian influenza. It mainly infects birds, but infections have also been confirmed in mammals such as humans and otters. Symptoms include loss of vitality, decreased food and water intake, decreased egg production rate, swelling of the face, discoloration of the crest and legs, cough, runny nose, diarrhea, etc.

[0046] The concentration of each plant extract contained in the cell entry inhibitor of the H5N1 subtype influenza virus of the present invention is not particularly limited. As the concentration of the ivy bright extract, for example, 0.1 to 300 μg / ml is preferable, 5 to 200 μg / ml is more preferable, and 15 to 150 μg / ml is even more preferable. As the concentration of the kasuri meti extract, for example, 0.1 to 300 μg / ml is preferable, 3 to 200 μg / ml is more preferable, and 5 to 150 μg / ml is even more preferable. As the concentration of the tartary buckwheat extract, for example, 3 to 300 μg / ml is preferable, 5 to 200 μg / ml is more preferable, and 8 to 150 μg / ml is even more preferable. As the concentration of the okra extract, for example, 3 to 300 μg / ml is preferable, 5 to 200 μg / ml is more preferable, and 15 to 150 μg / ml is even more preferable. As the concentration of the cinnamon extract, for example, 0.1 to 300 μg / ml is preferable, 0.5 to 200 μg / ml is more preferable, and 3 to 150 μg / ml is even more preferable. As the concentration of the shell ginger extract, for example, 15 to 300 μg / ml is preferable, 30 to 200 μg / ml is more preferable, and 50 to 150 μg / ml is even more preferable.

[0047] Hereinafter, the present invention will be specifically described by way of examples. Note that the present invention is not limited to these examples.

[0048] In this example, after preparing a cell entry inhibitor of a virus containing an extract obtained from the following materials, a virus cell entry inhibition test and a cell viability assay were performed using the cell entry inhibitor of the virus. The method for preparing the extract, the method for preparing the cell entry inhibitor of the virus, and the details and results of the test are described below.

[0049] [Example 1: Preparation of hot water extract] 1. 40 g of the following materials (materials with high water content were freeze-dried in advance) were placed in a 1 L Erlenmeyer flask, and 800 mL of pure water was added. 2. Heated on a hot plate, and extracted for 30 minutes after boiling. 3. After cooling with ice water, the extract was filtered through four layers of gauze or a 200-mesh nylon net. 4. The filtered extract was placed in a container with a bottom area of 400 cm ２The contents were placed in the stainless steel trays described above. At this time, the height from the bottom of the extract container to the water surface was kept to 2 cm or less. 5. The stainless steel trays were placed in a freeze-dryer and frozen at -40°C for 8 hours. 6. Vacuum drying was started at a shelf temperature of 25°C, and the contents were collected when the product temperature reached 25°C and the vacuum level stabilized. 7. The hot water extract was crushed and stored in a storage bottle with a desiccant.

[0050] (Ingredients) Eyebright, Fenugreek, Buckwheat, Okra, Cinnamon, Barberry, Ginger Lily

[0051] [Example 2: Preparation of viral cell entry inhibitors] Each obtained hot water extract was diluted to 1 mg / ml with Milli Q water. After filtering through a 0.45 μm filter, the stock solution and 10-fold serial dilutions (100 μg / ml, 10 μg / ml) were used in experiments.

[0052] [Example 3: Inhibition of viral cell entry using luciferase luminescence] A pseudotype virus (SARS2-pv) was prepared by attaching the SARS-CoV-2 spike protein to a vesicular stomatitis virus (pseudotyped vesicular stomatitis virus; VSVpv) that lacked the gene encoding the envelope protein by inserting the luciferase gene, according to a previously reported (Tani et al. Virol J (2021) 18:16). Furthermore, a pseudotyped virus (IAV-H5N1pv) was created by coating VSVpv with the hemagglutinin protein and neuraminidase protein of the H5N1 subtype influenza virus, based on a previously reported example (Cheresiz et al. Arch Virus (2014) 159:2651-2658). Angiotensin-converting enzyme 2 (ACE2) stable-expressing cell lines (used for SARS2-pv) or human embryonic kidney-derived cell lines (used for IAV-H5N1pv) were loaded onto a 96-well White / Clear Bottom Plate (Thermo Fisher Scientific) in 2 × 10⁻¹⁶ layers. ４Cells were seeded in cells / well. The following day, 10 μL of the test substance was mixed with 10 μL of SARS2-pv or IAV-H5N1pv, and after reacting at room temperature for 5 minutes, it was added to the cell culture supernatant (final concentrations: 100 μg / ml, 10 μg / ml, 1 μg / ml). After 24 hours of incubation, 20 μL / well of PikkaGene BrilliantStar-LT luminescence reagent (Toyo B-Net) was added, and after standing for 5 minutes, luciferase-mediated luminescence was measured using a GloMax Discover Microplane Reader. The cell entry inhibitory effect of SARS2-pv or IAV-H5N1pv was shown as a percentage relative to the luminescence intensity of the well (negative control) to which the hot water extract solvent Milli Q water was added, with the luminescence intensity set to 100%. The results are shown in Figures 1 and 2.

[0053] The results in Figure 1 show that the viral cell entry inhibitor of the present invention inhibits SARS-CoV-2 from entering cells by approximately 40-90%. The results in Figure 2 show that the viral cell entry inhibitor of the present invention inhibits H5N1 influenza virus from entering cells by approximately 20-60%.

[0054] [Example 4: Cell viability assay] 2 x 10 cells on a 96-well plate. ４ The day after seeding cells in cells / well, 10 μL of the test substance was added. After 24 hours of incubation, 10 μL / well of CellTiter 96 AQueos One Solution Reagent from CellTiter AQueos One Solution Cell Profitation Assay (Promega) was added, and the cells were incubated at 37°C under CO2. ２ After reacting in an incubator for one hour, the absorbance at 490 nm was measured. A well (negative control) containing only the culture medium with the test substance added was used as the background, and the background was subtracted for each test substance. The MTS assay values ​​are shown as a percentage with the value of the well (with solvent added) set to 100%. The results are shown in Figure 1.

[0055] The results shown in Figure 1 indicate that the virus cell entry inhibitor of the present invention has low toxicity, as it does not significantly affect cell viability.

Claims

1. A viral cell entry inhibitor comprising at least one selected from eyebright extract, fenugreek extract, buckwheat extract, okra extract, cinnamon extract, barberry extract, and ginger lily extract.

2. The virus cell entry inhibitor according to claim 1, wherein the virus is SARS-CoV-2.

3. An influenza virus cell entry inhibitor comprising at least one selected from eyebright extract, fenugreek extract, buckwheat extract, okra extract, cinnamon extract, and ginger lily extract.

4. The influenza virus cell entry inhibitor according to claim 3, wherein the influenza virus is an H5N1 subtype influenza virus.

5. A virus cell entry inhibitor according to any one of claims 1 to 4, which is a food or beverage, supplement or animal feed.

6. A pharmaceutical product, a virus cell entry inhibitor according to any one of claims 1 to 4.

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