KR20210014601A - Composition for preventing or treating coronavirus infection - Google Patents

Abstract

According to the present invention, it has been confirmed that at least one compound selected from the group of compounds represented by chemical formulas 1, 2 and 3 derived from Schisandra chinensis; isomers thereof; or pharmaceutically acceptable salts thereof have efficacy of inhibiting infection with coronavirus, more specifically novel coronaviruses, including MERS-CoV or SARS-CoV-2. Thus, the present invention provides a composition for preventing and treating corresponding diseases including the compounds as an active ingredient. The compounds show more excellent efficacy of inhibiting MERS-CoV or SARS-CoV-2 infection than chloroquine and lopinavir, which are antiviral agents used as positive controls.

Description

Pharmaceutical composition for preventing and treating coronavirus infection {Composition for preventing or treating coronavirus infection}

The present invention relates to a pharmaceutical composition for preventing or treating coronavirus infection using a compound derived from Schisandra chinensis as an active ingredient.

MERS (Middle East Respiratory Syndrome) is an acute respiratory disease caused by infection with MERS-CoV, a novel coronavirus (CoV) belonging to the beta coronavirus genus. MERS was first reported in Saudi Arabia in 2012, and since October 2016, 1,843 cases have occurred in 12 countries, with 705 deaths reported (Disease Management Headquarters 2016). Clinical characteristics include headache, sore throat, runny nose, muscle pain, loss of appetite, nausea, vomiting, abdominal pain, diarrhea, etc., with a focus on severe acute respiratory symptoms (fever, cough, shortness of breath, etc.), then respiratory failure, septic shock, It is known to have complications such as multiple organ failure. The origin of MERS-CoV has been identified as a bat, and MERS-CoV infected with bats infects camels and re-infects humans is accepted as the most promising transmission route (Zaki, van Boheemen et al. 2012).

On April 24, 2015, a 68-year-old male patient who visited the Middle East and returned to Korea after staying for 2 weeks was confirmed as the first MERS patient in Korea. In contact, multiple secondary infections occurred. The number of confirmed cases of MERS infection in 2015 was 185, of which a total of 36 died by September 2, 2015. Such an increase in the number of MERS infections caused enormous social and economic damages, and was an opportunity to reveal a major flaw in the national health care system.

On the other hand, COVID-19 (Coronavirus Disease-19, coronavirus infection-19) is a respiratory syndrome caused by infection with SARS-CoV-2, an RNA virus belonging to Coronaviridae. Since the first outbreak in Wuhan, Hubei Province, China in December 2019, COVID-19 has spread throughout China and around the world, and after infection, it has an incubation period of about 1-14 days, from mild to severe such as fever, malaise, cough, shortness of breath and pneumonia. Various respiratory infections have appeared, and other symptoms such as phlegm, sore throat, headache, hemoptysis, nausea, and diarrhea have been reported. The elderly, patients with reduced immune function, and patients with underlying diseases mainly increased or died, and the global fatality rate was about 5.4%, and the number of confirmed COVID-19 infections as of June 16, 2020 was 8,118,220. , Of which 439,156 died. In Korea, as of June 16, 2020, the number of confirmed cases was 12,155, and the number of deaths was 278, showing a mortality rate of 2.29%.

However, to date, there is no approved treatment effective for novel coronavirus infectious diseases including MERS and COVID-19. Therefore, by developing a composition for preventing and treating novel coronavirus infectious diseases through the present invention, it was intended to be used for prevention of MERS or COVID-19 infection, alleviating symptoms of MERS or COVID-19 infected patients, and improving the treatment rate.

On the other hand, Schisandrae Fructus is a dried ripe fruit of Schisandra chinensis Baill belonging to the Schisandraceae family. Schiznadra chinensis is a deep red color with a diameter of about 1cm in the shape of a ball. The inside contains 1~2 red juice and reddish brown seeds. There are five flavors: sweet, sour, bitter, salty, and spicy, and the sour taste is strong among them. Types include Schisandra (North Schisandra), South Schisandra, and Black Schisandra. Schisandra chinensis mainly grows in the Taebaeksan area, south schisandra chinensis in the southern islands, and black schisandra chinensis in Jeju Island. It is produced in Korea, Japan, Sakhalin Island, and China. Sizandrin, gomycin, citral, malic acid, citric acid, and other ingredients are used to strengthen the heart, lower blood pressure, and increase immunity.

Accordingly, the present inventors isolated the compound derived from Schisandra chinensis in the process of studying a substance for treating coronavirus, and confirmed that the isolated compound has excellent coronavirus treatment effect, thereby completing the present invention.

KR 101060794 B1

The present invention is any one or more compounds selected from the group of compounds represented by the formulas 1, 2 and 3 derived from Schizandra; Isomers thereof; Or its pharmaceutically acceptable salt; It is an object to provide a pharmaceutical composition for the prevention and treatment of novel virus infections including MERS or COVID-19, including as an active ingredient.

Another object of the present invention is any one or more compounds selected from the group of compounds represented by Formulas 1, 2 and 3; Isomers thereof; Or its pharmaceutically acceptable salt; It is to provide a composition for controlling the spread of novel viruses, including MERS or COVID-19, comprising as an active ingredient.

Another object of the present invention is any one or more compounds selected from the group of compounds represented by Formulas 1, 2 and 3; Isomers thereof; Or a pharmaceutically acceptable salt thereof; to provide a food composition for preventing or improving infection caused by coronavirus comprising as an active ingredient.

In addition, another object of the present invention is any one or more compounds selected from the group of compounds represented by Formulas 1, 2 and 3; Isomers thereof; Or a pharmaceutically acceptable salt thereof; to provide a veterinary composition for the prevention or treatment of infection by coronavirus comprising as an active ingredient.

The present invention is any one or more compounds selected from the group of compounds represented by the following formulas 1, 2 and 3; Isomers thereof; Or a pharmaceutically acceptable salt thereof; It provides a pharmaceutical composition for the prevention and treatment of virus infection comprising as an active ingredient.

<Formula 1> <Formula 2> <Formula 3>

More specifically, the virus is a middle east respiratory syndrome-coronavirus (MERS-CoV) or sascoronavirus-2 (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2).

The compound represented by Formulas 1, 2 and 3 is characterized in that it is isolated from the Schisandra chinensis extract or a fraction thereof.

In addition, the present invention is any one or more compounds selected from the group of compounds represented by Formulas 1, 2 and 3; Isomers thereof; Or a pharmaceutically acceptable salt thereof; provides a composition for controlling the spread of a virus comprising as an active ingredient, wherein the virus is Middle East Respiratory Syndrome-coronavirus (MERS-CoV) or Sascoronavirus- 2 (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2).

In addition, the present invention is any one or more compounds selected from the group of compounds represented by Formulas 1, 2 and 3; Isomers thereof; Or a pharmaceutically acceptable salt thereof; It provides a food composition for preventing or improving infection by coronavirus containing as an active ingredient, the food is characterized in that the food additive, beverage or beverage additive.

In addition, the present invention is any one or more compounds selected from the group of compounds represented by Formulas 1, 2 and 3; Isomers thereof; Or a pharmaceutically acceptable salt thereof; It provides a veterinary composition for preventing or treating infection caused by coronavirus, comprising as an active ingredient.

Through the present invention, a composition for inhibiting novel coronavirus infection including MERS or COVID-19 using a single compound derived from Schisandra was identified. The compounds identified in the present invention have superior efficacy and low cytotoxicity than existing antiviral agents effective in inhibiting MERS or COVID-19 infection.

FIG. 1 shows the results of the dose-dependent inhibition ratio of MERS-CoV infection and cell survival ratio (i) and the effect of suppressing MERS-coronavirus infection compared to the dose of Schizandrin B. .
FIG. 2 shows the results of the dose-dependent inhibition ratio of MERS-CoV infection and cell survival ratio (displayed by ▲) and the effect of inhibiting MERS-coronavirus infection compared to the dose of Gomysin N. .
FIG. 3 shows the results of the dose-dependent inhibition ratio of MERS-CoV infection and cell survival ratio (displayed ▲) and the effect of inhibiting MERS-coronavirus infection compared to the dose of Gomysin J .
FIG. 4 shows the results of the dose-dependent inhibition ratio of MERS-CoV infection and cell survival ratio (shown ▲) and the effect of inhibiting MERS-coronavirus infection compared to the dose of chloroquine.
Figure 5 shows the results of the MERS-coronavirus infection inhibitory effect (indicated by ●) and the cell survival rate (dose-dependent inhibition ratio of MERS-CoV infection and cell survival ratio; indicated by ▲) compared to the dose of Lopinavir (Lopinavir).
Figure 6 shows the results of the dose-dependent inhibition ratio of SARS-CoV-2 infection and cell survival ratio (shown ▲) and the effect of inhibiting Sascoronavirus-2 infection compared to the dose of Lopinavir Show.
7 shows the results of the dose-dependent inhibition ratio of SARS-CoV-2 infection and cell survival ratio compared to the dose of Sizandrin B.
8 shows the results of the dose-dependent inhibition ratio of SARS-CoV-2 infection and cell survival ratio compared to the dose of Gomysin N.
9 shows the results of the dose-dependent inhibition ratio of SARS-CoV-2 infection and cell survival ratio compared to the dose of Gomysin J.

The present invention relates to a composition for preventing, improving, controlling or treating the spread of a coronavirus comprising a lignan derivative isolated from an extract of Schisandra chinensis as an active ingredient.

Accordingly, the present invention provides a compound represented by the following formula A or a pharmaceutically acceptable salt thereof.

<Formula A>

More specifically, the compound represented by Formula A includes a compound represented by Formula 1, 2 or 3 below.

<Formula 1> <Formula 2> <Formula 3>

The compound represented by Formula A of the present invention may be isolated from an extract of Schisandra chinensis (Turcz.) Baill.

The Schisandra chinensis extract of the present invention can be extracted using a conventional solvent under conditions of a conventional temperature and pressure according to a conventional method known in the art for extracting an extract from a natural product. For example, in the present invention, the Schisandra chinensis extract is at least one selected from the group consisting of water, alcohols having 1 to 4 carbon atoms, ethyl acetate, acetone, butyl acetate, 1,3-butylene glycol, methylene chloride, and mixed solvents thereof. It can be extracted using a solvent.

In addition, a method of extracting the extract from Schizandra chinensis may be extracted through various methods such as room temperature extraction, hot water extraction, cold needle extraction, reflux extraction, and ultrasonic extraction, but is not limited thereto.

The prepared extract may be filtered, concentrated, or dried to remove the solvent, and filtration, concentration, and drying may be performed. For example, a filter paper or a vacuum filter may be used for filtration, a vacuum concentrator may be used for concentration, and a freeze-drying method may be performed for drying, but the present invention is not limited thereto.

Schisandra chinensis extract of the present invention is meant to include a fraction separated by further purifying the extract by the solvent. The fraction may be obtained by further performing a fractionation process with a solvent selected from the group consisting of butanol, hexane, methylene chloride, acetone, ethyl acetate, ethyl ether, chloroform, water, and a mixed solvent thereof. During the fractionation, the temperature may be 4° C. to 120° C., but is not limited thereto.

In addition, it is obvious to those skilled in the art that the compounds of the present invention have the same activity as those chemically synthesized and purified from natural products.

In the present invention, the compound can be obtained by a conventional method of separating and purifying a single compound from the Schisandra chinensis extract. For example, filtration using silica gel or celite gel columns, size-exclusion chromatography using liquid column chromatography, ion-exchange chromatography, partition chromatography, affinity ( affinity) chromatography or a combination of these chromatography can be used for separation and purification.

The compound of the present invention can be used in the form of a pharmaceutically acceptable salt, and an acid addition salt formed by a pharmaceutically acceptable free acid is useful. In the present invention, the term'pharmaceutically acceptable salt' is a concentration that is relatively non-toxic and harmless to patients, and side effects caused by this salt do not reduce the beneficial efficacy of the compound of formula A. It means an organic or inorganic addition salt. As these salts, inorganic acids and organic acids can be used as free acids, hydrochloric acid, bromic acid, nitric acid, sulfuric acid, perchloric acid, phosphoric acid, etc. can be used as inorganic acids, and citric acid, acetic acid, lactic acid, maleic acid, fumarin Acid, gluconic acid, methanesulfonic acid, glycolic acid, succinic acid, tartaric acid, galucturonic acid, embonic acid, glutamic acid, aspartic acid, oxalic acid, (D) or (L) malic acid, maleic acid, methanesulfonic acid, ethanesol Ponic acid, 4-toluenesulfonic acid, salicylic acid, citric acid, benzoic acid, malonic acid, and the like can be used. In addition, these salts include alkali metal salts (sodium salt, potassium salt, etc.) and alkaline earth metal salt (calcium salt, magnesium salt, etc.), and the like. For example, as an acid addition salt, acetate, aspartate, benzate, besylate, bicarbonate/carbonate, bisulfate/sulfate, borate, camsylate, citrate, edisylate, esylate, formate, fumarate, Gluceptate, Gluconate, Glucuronate, Hexafluorophosphate, Hybenzate, Hydrochloride/Chloride, Hydrobromide/Bromide, Hydroiodide/Iodide, Isethionate, Lactate, Malate, Mali Eate, malonate, mesylate, methyl sulfate, naphthylate, 2-naphsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogen phosphate, saccha Rate, stearate, succinate, tartrate, tosylate, trifluoroacetate, aluminum, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, Potassium, sodium, tromethamine, zinc salts, and the like may be included, among which hydrochloride or trifluoroacetate is preferred.

The compound of the present invention includes not only pharmaceutically acceptable salts, but also all salts, isomers, hydrates and solvates that can be prepared by conventional methods.

As used herein, the term “prevention” refers to any action that inhibits coronavirus or delays infection by administration of the pharmaceutical composition according to the present invention.

The term "treatment" used in the present invention means any action in which symptoms caused by coronavirus infection are improved or advantageously changed by administration of the pharmaceutical composition according to the present invention.

The pharmaceutical composition according to the present invention may further include a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier is commonly used in formulation, and includes, but is limited to, saline, sterile water, Ringer's solution, buffered saline, cyclodextrin, dextrose solution, maltodextrin solution, glycerol, ethanol, liposome, and the like. It is not, and other conventional additives such as antioxidants and buffers may be further included if necessary. In addition, diluents, dispersants, surfactants, binders, lubricants, and the like may be additionally added to prepare injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules or tablets. Regarding suitable pharmaceutically acceptable carriers and formulations, it can be preferably formulated according to each component using a method disclosed in Remington's literature. The pharmaceutical composition of the present invention is not particularly limited in its formulation, but may be formulated as an injection, an inhalant, an external preparation for skin, or the like.

The pharmaceutical composition of the present invention can be administered orally or parenterally (for example, intravenous, subcutaneous, intraperitoneal or topical application) according to a desired method, and the dosage is It depends on the degree, drug form, administration route and time, but may be appropriately selected by those skilled in the art.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type of disease, severity, drug activity, drug Sensitivity to, administration time, route of administration and rate of excretion, duration of treatment, factors including drugs used simultaneously, and other factors well known in the medical field. The pharmaceutical composition according to the present invention may be administered as an individual therapeutic agent or administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with a conventional therapeutic agent, and may be administered single or multiple. It is important to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects in consideration of all the above factors, and this can be easily determined by a person skilled in the art.

Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the patient's age, sex, condition, weight, absorption of the active ingredient in the body, inactivation rate and excretion rate, the type of disease, and drugs used in combination. 0.001 to 150 mg, preferably 0.01 to 100 mg per 1 kg of body weight may be administered daily or every other day, or divided into 1 to 3 times a day. However, since it may increase or decrease according to the route of administration, the severity of obesity, sex, weight, age, etc., the dosage amount does not limit the scope of the present invention in any way.

Hereinafter, a preferred embodiment is presented to aid the understanding of the present invention. However, the following examples are provided for easier understanding of the present invention, and the contents of the present invention are not limited by the following examples.

<Example>

Reversed-phase medium pressure liquid chromatography (RP-MPLC) and high-performance reverse-phase high-performance liquid chromatography (semi-preperative RP-HPLC) were performed to separate the compound from the Schisandra chinensis extract, or the methyl group removal reaction and /Or alkylation to obtain a compound represented by formula A. The separation and synthesis method as described above can be easily carried out by a general organic synthesis method for those of ordinary skill in the art.

For example, the following compounds were isolated, synthesized or purchased to conduct an effect test.

<Formula 1> <Formula 2> <Formula 3> schizandrin B Gomisin N Gomisin J

1. In vitro test method

1.1. Cell line and virus

Vero cells used in the present invention were purchased and used by the American Type Culture Collection (ATCC, CCL-81; Manassas, VA), 10% heat inactivated fetal bovine serum and 1× Antibiotic-Antimycotic (Gibco/Thermo Fisher Scientific, Waltham , MA) in Dulbecco's modified Eagle's medium (DMEM; Welgene, Gyeongsan, Korea) and cultured at 37°C under 5% carbon dioxide.

MERS-CoV Korean isolate (MERS-CoV/KOR/KNIH/002_05_2015, Genbank accession no. KT029139.1 [Kim et al., 2015 doi:10.1128/genomeA.00787-15]) from the Korea Centers for Disease Control and Prevention, National Institutes of Health It was provided and proliferated in vero cells according to the method suggested in prior literature (Kim et al., 2016 doi:10.1093/cid/ciw239).

SARS-CoV-2 (βCoV/KOR/KCDC03/2020) was provided by the Korea Centers for Disease Control and was cultured in vero cells. Viral titer for measuring cell viability was measured in vero cells by plaque assays.

All experiments using MERS-CoV and SARS-CoV-2 were carried out at the Pasteur Institute in Korea, which complied with the National Institutes of Health's enhanced biosafety level 3 (BL-3) containment procedure approved by the Korea Centers for Disease Control and Prevention. .

1.2. reagent

Chloroquine diphosphate (CQ; C6628) and Lopinavir (LPV; S1380) were purchased from SelleckChem (Houston, TX), and Lopinavir (LPV; GP6351) was purchased from Glentham Life Science (UK). The anti-MERS-CoV spike antibody and anti-SARS-CoV-2 N protein antibody used as primary antibodies were obtained from Sino Biological Inc. (Beijing, China). The secondary antibody Alexa Fluor 488 goat anti-rabbit IgG and the nuclear chromosome Hoechst 33342 were purchased from Molecular Probes/Thermo Fisher Scientific (Waltham, MA). 32% Paraformaldehyde (PFA) aqueous solution and normal goat serum were obtained from Electron Microscopy Sciences (Hatfield, PA) and Vector Laboratories, Inc. (Burlingame, CA).

1.3. Image-based assay using immunofluorescence assay

Since cells infected with MERS-CoV express viral proteins, they can be measured using antibodies that specifically bind to viral proteins. In the present invention, cells were stained using an antibody that binds to the spike protein of MERS-CoV, and the infected cells were imaged through a microscope. The infection rate (number of cells expressing the MERS-CoV spike protein/total number of cells) was measured with an internally developed Image Mining 3.0 (IM 3.0) plug-in. In order to compare the antiviral effects of the small molecule compounds, infected cells treated with dimethylsulfoxide (DMSO) were used as a negative control, and two compounds (CQ and LPV) with known antiviral activity against MERS-CoV were used as positive controls. The image-based assay was optimized.

1.4. Small molecule compound library

Low molecular weight compounds were dissolved in DMSO and stored at -80°C until analysis.

1.5. Image based Small molecule Compound screening ( MERS - CoV )

Vero cells in each well of 1.2 x ⁴ cells in Opti-PRO™ SFM containing 4 mM L-Glutamine and 1 x Antibiotic-Antimycotic in black, 384-well, micro-clear plates (Clear plates, Greiner bio-one, Kremsmunster, Austria). After 24 hours, the small molecule compound was added to each well using an automated liquid handling system (Apricot Designs, Covina, CA) before virus infection. The concentration of the solvent DMSO was maintained at 0.5% at the final concentration of the test compound. The compound was transferred to the treated BL-3 containment chamber and then infected with 0.0625 MOI of MERS-CoV. PFA was used 24 hours after infection (final PAF concentration = 4%) to fix the infection. After treatment with anti-MERS-CoV spike antibody on the immobilized cells, it was stained with Alexa Fluor 488 goat anti-rabbit IgG and Hoechst 33342. After fixation and staining of the infected cells, they were imaged on a fluorescence imaging system (Perkin Elmer Operetta, 20x, Waltham, MA) at 20x magnification. The infection rates for MERS-CoV of the cells treated with the low molecular weight compound were converted into the negative control group (0% infection inhibition rate) and the positive control group (100% infection inhibition rate) on each plate.

1.6. Dose-response curve (DRC) based assay using immunofluorescence assay (SARS-CoV-2)

24 hours before the experiment, add 1.2 × 10 ⁴ cells per well to Vero cells in DMEM containing 2% FBS and 1 × Antibiotic-Antimycotic solution (Gibco). Black, 384-well, μClear plates (Clear plates, Greiner bio-) one, Kremsmunster, Austria). Ten dose-response curves were generated at a concentration of 0.05 to 0.5 μM of the low molecular weight compound. In the case of viral infection, the plates were transferred to the BSL-3 containment chamber and then infected with 0.0125 MOI of SARS-CoV-2. Cells were fixed at 24 hpi with 4% PFA and analyzed by immunofluorescence assay. The acquired images were analyzed with internal software to quantify the cell number and infection rate, and antiviral activity was normalized to positive (mock) and negative (0.5% DMSO) controls in each plate. Dose-response curve is S-shaped according to the equation (response = minimum response + (maximum response-minimum response)/(1 + (IC ₅₀ / logarithmic value of concentration) ^{curve slope} ))) using XLfit 4 Software or Prism7 A curve is shown. IC ₅₀ values were calculated from normalized activity dataset-fit curves. All IC ₅₀ and CC ₅₀ values were measured in duplicate, and Z'-factor and percent coefficient of variation (%CV) were used as indicators.

2. In vitro test result

2.1. Image based Small molecule Compound screening ( MERS - CoV )

Positive control Chloroquine was measured with IC ₅₀ =29.78 μM, CC ₅₀ >150 μM, and Lopinavir with IC ₅₀ =16.29 μM and CC ₅₀ >50 μM. Shizandrin B measured IC ₅₀ =3.339 μM, CC ₅₀ =34.29 μM, Gomisin N measured IC ₅₀ =8.913 μM, CC ₅₀ >100 μM, Gomisin J measured IC ₅₀ =14.001 μM, CC ₅₀ =78.354 μM It was measured as.

2.2. Dose-response curve ( DRC ) base Assay (SARS- CoV -2)

Positive control Lopinavir was measured as IC ₅₀ =12.998 μM, CC ₅₀ >50 μM. Shizandrin B was measured with IC ₅₀ =13.39 μM, CC ₅₀ >50 μM, Gomisin N was measured with IC ₅₀ =22.39 μM, CC ₅₀ >50 μM, and Gomisin J with IC ₅₀ =28.16 μM, CC ₅₀ >50 μM It was measured as.

As a result of the experiment, it was confirmed that Shizandrin B, Gomisin N, and Gomisin B can be used as compositions for preventing and treating coronavirus infectious diseases, which are superior to the existing antiviral agents Choloroquine and Lopinavir.

<Formulation Example 1. Pharmaceutical formulation>

Formulation Example 1-1. Manufacture of tablets

20 g of the compound 3 of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch, and 32 g of colloidal silicic acid, respectively. After adding a 10% gelatin solution to this mixture, it was pulverized and passed through a 14 mesh sieve. This was dried, and 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate were added thereto, and the resulting mixture was made into tablets.

Formulation Example 1-2. Preparation of injection solution

100 mg of the compound 3 of the present invention, 0.6 g of sodium chloride, and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. This solution was put in a bottle and sterilized by heating at 20° C. for 30 minutes.

The above-described description of the present invention is for illustration purposes only, and those of ordinary skill in the art to which the present invention pertains can understand that it is possible to easily transform it into other specific forms without changing the technical spirit or essential features of the present invention. There will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not limiting.

Claims (11)

Any one or more compounds selected from the group of compounds represented by the following formulas 1, 2 and 3; Isomers thereof; Or a pharmaceutically acceptable salt thereof; a pharmaceutical composition for preventing and treating viral infections comprising as an active ingredient
<Formula 1><Formula2><Formula3>

The pharmaceutical composition of claim 1, wherein the compound is isolated from Schisandra chinensis extract or a fraction thereof.
The pharmaceutical composition of claim 1, wherein the virus is a parainfluenza virus (PIV), a respiratory syncytial virus (RSV), a rhinovirus, or a coronavirus.
The pharmaceutical composition of claim 3, wherein the virus is a coronavirus.
The method of claim 4, wherein the coronavirus is Middle East Respiratory Syndrome-coronavirus (MERS-CoV) or Sascoronavirus-2 (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2). Pharmaceutical composition characterized by
Any one or more compounds selected from the group of compounds represented by the following formulas 1, 2 and 3; Isomers thereof; Or a pharmaceutically acceptable salt thereof; a composition for controlling virus spread containing as an active ingredient
<Formula 1><Formula2><Formula3>

The composition of claim 6, wherein the virus is a coronavirus
The method of claim 6, wherein the coronavirus is Middle East Respiratory Syndrome-coronavirus (MERS-CoV) or Sascoronavirus-2 (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2). Composition characterized by
Any one or more compounds selected from the group of compounds represented by the following formulas 1, 2 and 3; Isomers thereof; Or a pharmaceutically acceptable salt thereof; a food composition for preventing or improving infection by coronavirus containing as an active ingredient
<Formula 1><Formula2><Formula3>

The food composition of claim 9, wherein the food is a food additive, a beverage or a beverage additive.
Any one or more compounds selected from the group of compounds represented by the following formulas 1, 2 and 3; Isomers thereof; Or a pharmaceutically acceptable salt thereof; a veterinary composition for preventing or treating infection caused by a coronavirus comprising as an active ingredient
<Formula 1><Formula2><Formula3>

Images