CN113975265A

CN113975265A - Application of apigenin in preparation of medicine for preventing and/or treating SARS-CoV-2 infection

Info

Publication number: CN113975265A
Application number: CN202111522304.0A
Authority: CN
Inventors: 张晗; 苗琳; 高秀梅; 张伯礼; 宋新波; 张俊华; 王跃飞; 李霖; 王彧; 陈璐
Original assignee: Tianjin University of Traditional Chinese Medicine
Current assignee: Tianjin University of Traditional Chinese Medicine
Priority date: 2021-12-13
Filing date: 2021-12-13
Publication date: 2022-01-28

Abstract

The application provides an application of apigenin in preparation of a medicine for preventing and/or treating new coronavirus infection. The apigenin can inhibit the combination of S protein of the new coronavirus and ACE2, so that the apigenin can be used for preventing and/or treating the infection of the new coronavirus, and further can be used for preparing a medicine for preventing and/or treating the infection of the new coronavirus. Further, the pharmaceutical composition comprising apigenin can also be used for preparing a medicament for preventing and/or treating a new coronavirus infection.

Description

Application of apigenin in preparation of medicine for preventing and/or treating SARS-CoV-2 infection

Technical Field

The application relates to the technical field of medicines, in particular to application of apigenin in preparing a medicine for preventing and/or treating SARS-CoV-2 infection.

Background

The novel coronavirus (SARS-CoV-2, new coronavirus for short) is a novel beta coronavirus, and the transmission mode is presumed to be that the coronavirus is transmitted by animals and then interpersonal transmission is carried out; respiratory droplets and close contact transmission are the main transmission routes, and the possibility of transmission through aerosol exists under the condition of long-term exposure to high-concentration aerosol in a relatively closed environment, so that the respiratory droplets and the close contact transmission have strong infectivity and high pathogenicity, and form a great threat to human health. With the rapid development of epidemic situation, the development of anti-SARS-CoV-2 drugs is imminent.

SARS-CoV-2 can be combined with respiratory Angiotensin converting enzyme 2 (ACE 2) to infect cells through spike glycoprotein (S protein), the S protein on the surface of SARS-CoV-2 is a key protein of corresponding receptors on virus recognition target cells, and the S protein is effectively combined with ACE2 on the surface of human cells, so that novel coronavirus pneumonia (COVID-19, abbreviated as new coronary pneumonia) and Acute Respiratory Distress Syndrome (ARDS) are caused, and the condition of part of patients is changed sharply in a short period, and organ failure and even death occur. The S protein of SARS-CoV-2 is divided into two subunits, S1 and S2, the S1 subunit includes N-terminal domain (NTD) and C-terminal domain (CTD), wherein the CTD has the function of receptor recognition and binding, also called Receptor Binding Domain (RBD); ACE2 is a peptidase belonging to type I transmembrane protein, and is mainly distributed in type II alveolar cells in lung tissues, and is distributed in small amount in type I alveolar cells, airway epithelial cells, fibroblasts, endothelial cells and macrophages; the RBD domain on the S1 subunit is responsible for binding to ACE2 on the host cell, further fusing with the cell membrane of the host to infect humans. Therefore, blocking the binding of the S protein and ACE2 is one of the important directions for treating COVID-19, and the aim of preventing virus infection of human body is achieved by blocking or competitively inhibiting the binding of the S protein and ACE 2. Lopinavir and ritonavir have been used in clinical COVID-19 therapy, but due to their great side effects, the search for new safe specific drugs is at hand.

The existing research shows that the apigenin has the effects of resisting inflammation, resisting tumor, regulating immunity and the like, but other pharmacological effects of the apigenin are not clear.

Disclosure of Invention

Through intensive research, the inventor of the application finds that apigenin can inhibit the binding of S protein of the new coronavirus and ACE2, so that apigenin can be used for preventing and/or treating the infection of the new coronavirus, and further used for preparing a medicine for preventing and/or treating the infection of the new coronavirus.

A first aspect of the application provides the use of apigenin in the manufacture of a medicament for the prevention and/or treatment of a new coronavirus infection.

A second aspect of the present application provides a pharmaceutical composition for preventing and/or treating a new coronavirus infection, comprising apigenin.

The apigenin can inhibit the combination of S protein of the new coronavirus and ACE2, so that the apigenin can be used for preventing and/or treating the infection of the new coronavirus, and further can be used for preparing a medicine for preventing and/or treating the infection of the new coronavirus. Further, the pharmaceutical composition comprising apigenin can also be used for preparing a medicament for preventing and/or treating a new coronavirus infection.

Drawings

In order to more clearly illustrate the technical solutions of the present application, the drawings required for the present application will be briefly described below, and it is apparent that the drawings in the following description are only one embodiment of the present application, and it is obvious for those skilled in the art that other embodiments can be obtained according to the drawings.

FIG. 1A shows the results of the inhibition rate of apigenin on the binding of S protein and ACE2 receptor at different concentrations;

FIG. 1B is a graph of the inhibition rate of apigenin inhibiting the binding of S protein to ACE2 receptor;

FIG. 2A shows the results of luciferase activity of apigenin inhibiting pseudovirus infection of Opti-HEK293/ACE2 cells;

FIG. 2B is a graph showing the inhibition rate of apigenin in inhibiting pseudovirus infection of Opti-HEK293/ACE2 cells.

Detailed Description

The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all of the embodiments. All other embodiments that can be derived by one of ordinary skill in the art from the description herein are intended to be within the scope of the present disclosure.

The inventor finds in research that the apigenin can inhibit the binding of S protein of the new coronavirus and ACE2, so that the apigenin can be used for preventing and/or treating the infection of the new coronavirus, and further can be used for preparing a medicament for preventing and/or treating the infection of the new coronavirus.

The term "treatment" has its ordinary meaning in the present application and in the present application especially refers to the treatment of a mammalian subject (preferably a human) already suffering from a new coronavirus infection with a drug according to the present application in order to obtain a therapeutic, curative, palliative etc. effect on said disease. Similarly, the term "prevention" as used herein has its ordinary meaning and in this application refers in particular to the treatment of a mammalian subject who may be suffering from or at risk of suffering from a new coronavirus infection with a medicament of the present application in order to expect a preventive, prophylactic, deterrent, abrogating etc. effect on said disease.

In some embodiments, the neocoronavirus infection comprises at least one of pneumonia and acute respiratory distress syndrome caused by a neocoronavirus infection.

In some embodiments, apigenin prevents and/or treats a new coronavirus infection by inhibiting the binding of the new coronavirus S protein to host ACE 2.

In some embodiments, the apigenin is provided in the form of a monomer, or in the form of a plant extract comprising the same.

In some embodiments, the plant extract is selected from at least one of a giant knotweed extract and a verbena extract.

The extraction method of the polygonum cuspidatum extract and the verbena extract is not particularly limited, and a person skilled in the art can extract the polygonum cuspidatum extract and the verbena extract by the prior art, and exemplarily, the verbena extract can be subjected to reflux extraction by using 60-80% methanol or ethanol to obtain the verbena extract containing apigenin.

In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.

In the present application, "pharmaceutically acceptable" means having no substantial toxic effect when used in the usual dosages, and thus being approved by the government or equivalent international organization or approved for use in animals, more particularly in humans, or registered in the pharmacopoeia.

The "pharmaceutically acceptable carrier or excipient" useful in the pharmaceutical compositions of the present application may be any conventional carrier in the art of pharmaceutical formulation, and the selection of a particular carrier will depend on the mode of administration or the type and state of the disease used to treat a particular patient. The preparation of suitable pharmaceutical compositions for a particular mode of administration is well within the knowledge of those skilled in the pharmaceutical art. For example, solvents, diluents, disintegrants, precipitation inhibitors, surfactants, glidants, binders, lubricants, dispersants, suspending agents, isotonic agents, thickeners, emulsifiers, stabilizers, hydrating agents, emulsification accelerators, buffers, absorbents, colorants, ion exchangers, mold release agents, coating agents, flavors, antioxidants, and the like, which are conventional in the pharmaceutical field, may be included as the pharmaceutically acceptable carrier or excipient. If necessary, a flavor, a preservative, a sweetener and the like may be further added to the pharmaceutical composition.

The term "pharmaceutical composition" as used herein has its ordinary meaning. In addition, the "pharmaceutical composition" of the present application may also be present or provided in the form of a health product, a functional food, a food additive, or the like. The pharmaceutical compositions of the present application can be prepared by conventional techniques in the pharmaceutical field, particularly in the formulation field, by obtaining the active ingredients of the raw materials of the pharmaceutical compositions of the present application by extraction, separation and purification means commonly used in pharmaceutical manufacturing, optionally mixing with one or more pharmaceutically acceptable carriers or excipients, and then forming the desired dosage form. The pharmaceutical composition according to the present application is a pharmaceutical preparation which can be suitably used for oral administration, a pharmaceutical preparation (e.g., solution) suitable for parenteral injection (e.g., intravenous injection, subcutaneous injection), a pharmaceutical preparation (e.g., ointment, patch or cream) suitable for surface administration, or a pharmaceutical preparation (e.g., suppository) suitable for rectal administration, and the like. Dosage forms for oral administration may include, for example, tablets, pills, drop pills, hard or soft capsules, solutions, suspensions, emulsions, tinctures, syrups, powders, fine granules, pellets, elixirs and the like, without being limited thereto. In addition to the active ingredient, these preparations may contain diluents (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and glycine), lubricants (e.g., silica, talc, stearic acid or its magnesium salt, calcium salt, and polyethylene glycol). Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, and polyvinylpyrrolidone. If necessary, it may further contain pharmaceutically acceptable additives such as disintegrating agents (e.g., starch, agar, alginic acid or sodium salt thereof), absorbents, coloring agents, flavoring agents, sweetening agents, and the like. Tablets may be prepared according to conventional mixing, granulating or coating methods.

The pharmaceutical composition of the present application, in a pharmaceutically acceptable dose of apigenin, i.e., an administration dose, may vary according to the age, sex and weight of a subject to be treated, a specific disease or pathological state to be treated, the severity of the disease or pathological state, the administration route, and the judgment of a diagnostician. Determining the dosage to be administered taking these factors into account is within the level of skill in the art. A typical dose may be 0.01-1000 mg/kg/day, specifically 1-100 mg/kg/day. However, the scope of the present disclosure is not in any way limited by the administration dosage.

The present application will be described in detail with reference to specific examples.

Apigenin (CAS number: 520-36-5), available from Douglas Biotechnology, Inc., has the following structural formula:

the experimental materials and methods used in the following examples are, unless otherwise specified, conventional materials and methods.

Example 1 molecular docking method to predict the interaction of apigenin with the S protein, ACE2 receptor

Preparing small molecular ligand apigenin: downloading the 3D structure of the apigenin from http:// www.chemspider.com/; and (3) completing the structure: adopting Discovery Studio 2020 software, expanding Small Molecules/Prepare or Filter Ligands in a toolbar, clicking the Prepare Ligands, generating a three-dimensional structure of apigenin by the operation, and hydrogenating to generate isomers and the like; optimizing the structure: expand Small Molecules/Minimize Ligands in toolbar, click on Full Minimization (parameters typically use defaults); and (5) storing the optimized small molecular structure.

Preparation of macromolecular receptor: the 3D structure of the S protein-ACE 2 receptor complex was downloaded from a protein database (http:// www.rcsb.org /), and the PDB accession number: 6LZG (resolution: 2.50A °); and (3) macromolecular optimization treatment: opening Discovery Studio 2020 software, expanding Macromolecules/Prepare Protein/Manual Preparation in a tool bar, clicking clear Protein, expanding Macromolecules/Prepare Protein/Automatic Preparation in the tool bar, clicking the Prepare Protein, deleting water molecules and heteroatoms, hydrogenating, dehydrating, completing a structure, setting a protonation state and the like; the optimized receptor structure is stored as a "6 LZG + prep" file.

Definition of the active center of the receptor: it has been reported that the S protein of SARS-CoV-2 can bind to the human ACE2 receptor, thereby causing the virus to invade the human body. In this example, the protein-protein interaction (PPI) between the S protein and ACE2 in the S protein-ACE 2 receptor complex was first analyzed, and the sites (Site) that may disrupt the binding of the S protein to ACE2 were identified; as shown in Table 1, the action sites on the two binding interfaces can be divided into three regions, the three regions comprise six binding sites, the active centers are respectively defined according to the amino acid positions of the different binding sites, namely S-site1, S-site2, S-site3, ACE2-site1, ACE2-site2 and ACE2-site3, and the receptor structures after the active centers are defined are additionally stored as 6LZG + prep + active files.

TABLE 1

The active site of binding of the S protein-ACE 2 receptor complex to each other was determined according to table 1: according to the interaction between S protein and ACE2 receptor, the binding Site can be divided into three regions, namely Site1, Site2 and Site 3; the Site1 region consists of the interaction of TYR449, GLY496, GLN498, THR500, ASN501, GLY502, TYR505 residues on the S protein with GLN42, LYS353, GLY354, ASP355 residues on the ACE2 receptor surface; the Site2 region consists of LYS417, GLN493, LEU455 residues on the S protein interacting with ASP30 and HIS34 residues on the surface of ACE2 receptor; the Site3 region consists of the interaction of GLU484, PHE486, ASN487, TYR489 residues on the S protein with GLN24, PHE28, LYS31, MET82, TYR83 residues on the surface of the ACE2 receptor.

Performing CDOCKER molecular docking on the optimized structure of apigenin and an active center defined by an S protein-ACE 2 complex respectively; storing and analyzing the 2D graph of the docking result; using the binding ENERGY (Interactive ENERGY) as a score, generally, the lower the value of the binding ENERGY, the stronger the binding affinity of the compound to form a stable complex with S protein-ACE 2, and thus, the stronger the binding inhibition of S protein-ACE 2 was shown. The results of the binding energy of apigenin with ACE2 and S protein are shown in Table 2, and the results show that apigenin can be respectively bound with three sites of ACE2, wherein the binding with Site1 is better, and the value of the binding energy is-35.46 kJ/mol; apigenin can be combined with three sites of S protein respectively, wherein the Site2 is better combined, and the binding energy value is-40.55 kJ/mol.

TABLE 2

The amino acid residues of apigenin, SARS-CoV-2 surface S protein and ACE2 receptor are shown in Table 3; wherein apigenin and ACE2 protein residues LYS353, GLY354 and ASP355 form attractive charge, hydrogen bond and Anion-Pi (Pi-Anion) action respectively at Site 1; t-shaped (pi-pi T-shaped) interactions, hydrogen bonds and salt bridges that form pi-pi bonds with S protein residues TYR449, GLN498, ARG404, respectively; the Site2 and ACE2 protein residue HIS34 form Pi-Pi stacking (Pi-Pi stacked) effect; forms Pi-Alkyl (Pi-Alkyl) hydrophobic interaction with S protein residues LYS417 and LEU455 respectively; hydrogen bonds, salt bridges, Pi-Alkyl hydrophobic effect and Pi-Pi stacked effect are respectively formed between Site3 and ACE2 protein residues LYS31 and TYR 83; the formation of an Anion-Pi (Pi-Anion) interaction with the S protein residue GLU484 may disrupt the formation of electrostatic interactions between the ACE2 protein LYS31 and the S protein GLU 484. The results show that apigenin can be combined with an S protein site and an ACE2 receptor site.

TABLE 3

Example 2 Effect of apigenin on binding of S protein to ACE2 receptor

The detection kit for the SARS-CoV-2 neutralizing antibody has the following principle: the kit is a neutralizing antibody blocking ELISA (enzyme linked immunosorbent assay) detection tool, and comprises two key components: HRP (horse radish peroxide) labeled RBD fragment of recombinant SARS-CoV-2 and human ACE2 receptor protein (hACE 2); the combination of RBD antigen of S protein binding structure domain of SARS-CoV-2 and ACE2 antigen of receptor protein is used to simulate the interaction between virus and host cell, and the virus infection is judged by chromogenic reaction, but when neutralizing antibody exists, the interaction between S protein and ACE2 receptor is blocked, and the chromogenic reaction is weakened.

1) Dissolution of monomer components: dissolving apigenin in dimethyl sulfoxide (DMSO, Beijing Solebao Tech Co., Ltd.) to obtain monomer solutions with concentration of 100mM (mmol/L), 50mM, 20mM, 10mM, 5mM, and 2.5 mM; 2) using a SARS-CoV-2 neutralizing antibody detection kit (Cat.No.: L00847-A, Nanjing Kingsry Biotech Co., Ltd.), the temperature was returned to room temperature before use; 3) diluting the monomer solution of the apigenin, the positive control and the negative control in the kit by using a sample diluent in the kit according to a ratio of 1:9, wherein the concentrations of the diluted apigenin are 10mM, 5mM, 2mM, 1mM, 0.5mM and 0.25mM respectively; 4) mixing the diluted monomer solution, negative control and positive control with RBD fragment (HRP-RBD) of horseradish peroxidase labeled recombinant SARS-CoV-2 at volume ratio of 1:1 to obtain 100 μ L of each complex mixture, and incubating at 37 deg.C for 30 min; 5) respectively adding 100 mu L of each compound mixed solution into an enzyme label plate coated with ACE2 to obtain each monomer administration group, a negative control group and a positive control group, covering the plate with a cover plate film, and then incubating for 15 minutes at 37 ℃; wherein the final concentration of apigenin of each monomer administration group is 5mM, 1mM, 0.5mM, 0.25mM and 0.125mM respectively; 6) the cover plate membrane was removed and the plate washed 4 times with 260. mu.L of 1 Xwash solution; 7) adding 100 mu L of TMB solution into each hole, and incubating for 15 minutes at 20-25 ℃ in the dark; 8) adding 50 mu L of stop solution into each hole to stop the reaction; 9) immediately after termination, the samples were analyzed by microplate reader (diken (shanghai) trade ltd, model: INFINITEF50) at 450 nm.

According to the light absorption value, by the formula: calculating the inhibition rate of apigenin on the combination of S protein and ACE2 receptor, wherein the inhibition rate is 1-absorbance value of monomer administration group/absorbance value of negative control group multiplied by 100%; wherein, the results of the inhibition rate of apigenin with different concentrations on the combination of S protein and ACE2 receptor are shown in figure 1A(ii) a The results of obtaining an inhibition rate curve are shown in fig. 1B, with lg (apigenin concentration (mM)) as the abscissa and the inhibition rate as the ordinate; the results in FIG. 1A and FIG. 1B show that apigenin can inhibit the binding of the S protein of SARS-CoV-2 to ACE2 receptor in a concentration-dependent manner, wherein the inhibition rate at 5mM is 43.07%; further calculation of the semi-Inhibitory Concentration (IC)₅₀) Numerical values, results show the IC of apigenin₅₀The value was 0.59 mM. The results show that apigenin inhibits the binding of S protein and ACE2 receptor in a concentration-dependent manner, and apigenin inhibits the IC of the binding of S protein and ACE2 receptor₅₀The value was 0.59 mM.

Example 3 Effect of apigenin on infection of Opti-HEK293/ACE2 cells by pseudoviruses

The principle of the pseudovirus neutralizing antibody detection kit is as follows: the envelope glycoprotein in the lentiviral vector is replaced by the new coronavirus S protein to form a pseudovirus simulating the infection of the new coronavirus; the pseudovirus infects target cells through surface S protein and expresses a reporter luciferase gene, and the blocking degree of the virus can be deduced by detecting the expression quantity of the reporter gene luciferase, so that the neutralizing agent is screened or verified; neutralizing agents (e.g., antibodies) can block the binding of the S protein to ACE2, thereby preventing infection of the host cell by the pseudovirus.

The SARS-CoV-2 pseudovirus neutralization detection kit (Nanjing Kingsry Biotechnology Co., Ltd.) was used: 1) preparation of monomer components: dissolving apigenin in DMSO, and preparing monomer solution with concentration of 400 μ M, 160 μ M, 100 μ M, 40 μ M, and 20 μ M in Opti-MEM culture medium; 2) preparation of positive antibody: adding 5 mu L of 1 mu g/mu L of positive antibody into 120 mu L of Opti-MEM culture medium to prepare a positive antibody solution of 40 mu g/mL; 3) taking pseudovirus (from the kit), placing the pseudovirus in a water bath at 37 ℃ for rapid re-melting, adding the virus into a 15ml centrifuge tube containing 1500 mu L of Opti-MEM culture medium, and uniformly mixing to obtain a pseudovirus solution; 4) in each monomer administration group, monomer solution with each concentration is added into each group at 25 mu L/hole; adding a positive antibody solution into the positive control group at a rate of 25 mu L/hole; adding 25 μ L of Opti-MEM culture medium into the negative control group and the blank control group respectively; adding 25 mu L/hole pseudovirus solution into the monomer administration group, the positive control group and the negative control group respectively, and adding 25 mu L/hole Opti-MEM culture medium into the blank control group; wherein the final concentration of apigenin in each monomer administration group is 200 μ M, 80 μ M, 50 μ M, 20 μ M and 10 μ M respectively; 5) respectively mixing with pseudovirus solution, and incubating at room temperature for 1 h; 6) placing an Opti-HEK293/ACE2 cell (derived from the kit, namely an HEK293 cell over expressing ACE2) in a water bath at 37 ℃ to rapidly re-fuse the cell; 7) transferring the cells to a 15ml centrifuge tube, adding 4ml of preheated DMEM complete culture medium, centrifuging at 100 Xg for 5min, and discarding the supernatant; 8) suspending the cells in 4ml of pre-warmed DMEM complete medium, fully mixing, counting the cells and adjusting the density of the cell suspension to 600000 cells/ml; 9) after the incubation in the step 5) is finished, adding 50 mu l of the cell suspension in the step 8) into each hole; after the edge hole of the 96-well plate is sealed by PBS, putting the 96-well plate into a cell culture box; 10) adding 50 mu L of preheated fresh DMEM complete culture medium into each hole after 24 hours, and continuously putting the mixture into an incubator for 24 hours; 11) sealing the 96-hole cell culture microporous plate with the white wall and the transparent bottom by using a microporous plate sealing film; carefully absorbing and discarding the culture medium of the 96-well plate, immediately adding 50 mul of newly-prepared luciferase developing solution, and incubating for 3-5 minutes at room temperature; 12) the microplate luminescence detector detects the chemiluminescence value, and the signal value is read, namely the luciferase activity result.

The data obtained were statistically analyzed using the software GraphPad Prism 8.0.1 and Excel, all values being expressed as mean ± SD, and statistical comparisons were performed using paired t-tests, one-way analysis of variance (ANOVA). P is less than 0.05, which is significant.

The luciferase activity of each group is counted, and the result is shown in fig. 2A, compared with the negative control group, apigenin (such as the administration group with the final concentration of 200 μ M) can reduce the luciferase activity of Opti-HEK293 cells after over-expressing ACE2, which indicates that apigenin can effectively prevent pseudovirus from entering the cells (n ═ 3 × P < 0.01, compared with the negative control group); from the read signal values, by the formula: the inhibition rate is 1- (signal value of monomer administration group-signal value of blank control group)/(signal value of negative control group-signal value of blank control group) × 100%, the inhibition rate of apigenin on pseudovirus-infected cells is obtained by calculation, and the inhibition rate of apigenin on pseudovirus-infected cells is plotted by using lg (apigenin concentration (μ M)) as abscissa and using apigenin on ordinate to obtainThe inhibition curve results are shown in FIG. 2B, and IC is further calculated₅₀Numerical value, result display IC₅₀The value was 69.32. mu.M. The results show that apigenin can inhibit pseudovirus containing the S protein of the new coronavirus from infecting Opti-HEK293/ACE2 cells, and apigenin inhibits IC of the pseudovirus from infecting Opti-HEK293/ACE2 cells₅₀The value was 69.32. mu.M.

In conclusion, apigenin can inhibit the combination of new coronavirus S protein and ACE2 and inhibit pseudovirus infected cells containing the new coronavirus S protein, so that apigenin can inhibit the combination of the new coronavirus S protein and host ACE2, can be used for preventing and/or treating new coronavirus infection and can be further used for preparing a medicine for preventing and/or treating the new coronavirus infection.

The above description is only for the preferred embodiment of the present application and is not intended to limit the scope of the present application. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present application are included in the protection scope of the present application.

Claims

1. The use of apigenin in preparing medicine for preventing and/or treating SARS-CoV-2 infection is provided.

2. The use of claim 1, wherein the SARS-CoV-2 infection comprises at least one of pneumonia and acute respiratory distress syndrome caused by SARS-CoV-2 infection.

3. The use as claimed in claim 1, wherein apigenin prevents and/or treats SARS-CoV-2 infection by inhibiting the binding of SARS-CoV-2S protein and host ACE 2.

4. A pharmaceutical composition for preventing and/or treating SARS-CoV-2 infection, comprising apigenin.

5. The pharmaceutical composition of claim 4, wherein the apigenin is provided in the form of a monomer or a plant extract containing the same.

6. The pharmaceutical composition of claim 5, wherein the plant extract is selected from at least one of a giant knotweed extract and a verbena extract.

7. The pharmaceutical composition of any one of claims 4-6, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.

8. The pharmaceutical composition according to claim 7, wherein the pharmaceutically acceptable carrier or excipient is selected from at least one of a solvent, a diluent, a disintegrant, a precipitation inhibitor, a surfactant, a glidant, a binder, a lubricant, a dispersant, a suspending agent, an isotonicity agent, a thickener, an emulsifier, a preservative, a stabilizer, a hydrating agent, an emulsification accelerator, a buffer, an absorbent, a colorant, a flavoring agent, a sweetener, an ion exchanger, a mold release agent, a coating agent, a flavoring agent, or an antioxidant.

9. The pharmaceutical composition of any one of claims 4-6, wherein the pharmaceutical composition is formulated as any one of a powder, a tablet, a capsule, a pill, a drop pill, an emulsion, a suspension, or a tincture.