Application of higenamine in the prevention and treatment of new coronavirus

Abstract

The present invention provides the use of higenamine in preventing and treating the novel coronavirus, belonging to the field of traditional Chinese medicine application technology. Higenamine can target host factors and, as an activator of host factors, inhibit the replication of the novel coronavirus. It has broad-spectrum antiviral activity and plays an important role in the prevention and treatment of the novel coronavirus. Compared with existing novel coronavirus treatment drugs, the compounds of the present invention have different antiviral mechanisms of action and are a beneficial supplement to existing antiviral drugs, providing a new option for antiviral treatment drugs.

Description

Technical Field

[0001] The present invention relates to the technical field of application of traditional Chinese medicine, and in particular to the application of higenamine in preventing and treating the novel coronavirus. Background Art

[0002] Since the outbreak of the new coronavirus (SARS-CoV-2), it has caused a global epidemic. Because it is highly contagious, highly mutable, and can cause severe respiratory diseases, it is considered the most serious public health threat in recent years.

[0003] With the development and application of vaccines and small molecule drugs, the epidemic has been brought under control to a certain extent. The small molecule drugs currently reported for the treatment of COVID-19, such as remdesivir, VV116, nematevir / ritonavir, etc., are all drugs designed for viruses. However, due to the characteristics of continuous mutation of RNA viruses, the new coronavirus has continued to mutate in just three years, from the initial wild strain to the Delta strain, to Omicron, and then to the recent XBB and EG5. As the virus mutates, the effects of vaccines and small molecule drugs are becoming increasingly limited, so the development of a broad-spectrum antiviral drug is urgently needed. Summary of the Invention

[0004] In view of the above-mentioned deficiencies in the prior art, in order to provide a safe, effective and broad-spectrum drug, the present invention provides the use of demethyl-coclaurine having the following structure in the preparation of drugs for preventing and treating the new coronavirus:

[0005] .

[0006] The present invention mainly targets host factors, and affects host factors by higenamine having the structure shown above, thereby inhibiting the proliferation of the new coronavirus. It has good broad spectrum and can effectively avoid viral mutation.

[0007] Preferably, the new coronavirus is selected from the new coronavirus wild strain (WT) or the new coronavirus BA.5 strain.

[0008] Preferably, the concentration of higenamine in the drug for preventing and treating the new coronavirus is ≥0.01wt%.

[0009] The molecular formula of higenamine is C 16 H 17 NO3, molecular weight is 271.31.

[0010] Preferably, the drug for preventing and treating the new coronavirus includes the compound or pharmaceutically acceptable salt of the compound used in the above application, and a pharmaceutically acceptable adjuvant.

[0011] Preferably, the pharmaceutically acceptable excipient includes one or more pharmaceutically acceptable carriers, excipients or diluents.

[0012] Preferably, the dosage form of the drug includes at least one of tablets, capsules, aqueous or oily suspensions, granules, emulsions, oral solutions, injections or powders.

[0013] Preferably, the medicine further comprises at least one other anti-coronavirus active ingredient.

[0014] Preferably, the administration of the drug includes at least one of oral, intratumoral, rectal, parenteral injection and local administration.

[0015] The present invention abandons the conventional small molecule drugs designed to target the virus itself, and instead targets host factors to achieve antiviral effects. The present invention uses third-generation sequencing to screen the host factor actinin A4 (ACTN4) recombinant protein, and found that ACTN4 has a good antiviral effect at the cellular level. Further mechanism studies have found that (such as Figure 1 As shown in Figure 3 ), ACTN4 inhibits the binding of nsp7 and / or nsp8 to nsp12, thereby reducing the amount of nsp12 bound to the 2019-nCoV genome and thereby inhibiting the replication of the 2019-nCoV. Higenamine was screened as an agonist of ACTN4 targeting ACTN4. During the 2019-nCoV replication process, nsp7, nsp8, and nsp12 are all minimal replicons. nsp7 and nsp8 bind first, then recruit nsp12 to form a complex, which then binds to the 2019-nCoV RNA to initiate viral replication. However, after the new coronavirus infects cells, it leads to a decrease in the methyltransferase WTAP, which in turn leads to a decrease in the m6A modification on the ACTN4 mRNA, thereby affecting the degradation and translation of RNA, thereby inhibiting the expression of ACTN4. Therefore, higenamine, as an agonist of ACTN4, can upregulate the expression of ACTN4. ACTN4 can bind to the N-terminus of nsp12. After the increase in ACTN4, it binds to more nsp12, causing ACTN4 to compete with nsp7 and / or nsp8 for nsp12, resulting in a decrease in nsp12 bound to the new coronavirus RNA, thereby inhibiting the replication of the new coronavirus.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] (1) In view of the fact that RNA viruses are prone to mutation, we will focus our drug development not on the virus itself, but on host factors. Without affecting the normal life activities of cells, we can inhibit viral replication by changing the expression of host factors. This has better broad-spectrum and better avoids the problem of viral mutation.

[0018] (2) Most of the previous research on viral drug development and vaccine development focused on the design or modification of the virus itself. This invention provides new ideas for future drug development and vaccine development. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Diagram of the mechanism by which ACTN4 regulates SARS-CoV-2 replication.

[0020] Figure 2 This is the flowchart of third-generation sequencing.

[0021] Figure 3 Figure 2. Knockdown of ACTN4 promotes the replication of the novel coronavirus.

[0022] Figure 4 Diagram showing how overexpression of ACTN4 inhibits the replication of the novel coronavirus.

[0023] Figure 5 Diagram showing that higenamine inhibits the replication of the new coronavirus.

[0024] Figure 6 Flowchart of animal experiments.

[0025] Figure 7 This is a graph showing the inhibition of viral load in lung tissue by higenamine.

[0026] Figure 8 This is a graph showing the inhibition of viral load in brain tissue by higenamine.

[0027] Figure 9 The following are the results of HE staining of lung tissue and brain tissue. DETAILED DESCRIPTION

[0028] The technical scheme of the present invention is further described below through examples. The raw materials used in the examples can be purchased from the market or prepared by conventional methods.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one skilled in the art to which this invention pertains. The terms used in this specification of the present invention are for the purpose of describing specific embodiments only and are not intended to limit the present invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0030] The genetic sequence of SARS-CoV-2 is similar to that of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), and its binding to and entry into host cells is mainly related to the S protein.

[0031] The S protein contains S1 and S2 subunits, where the S1 subunit contains the receptor binding domain (RBD) for binding to the cellular receptor, aminopeptidase N (APN); the S2 subunit, which consists of fusion peptide (FP), heptad repeat 1 (HR1), heptad repeat 2 (HR2), transmembrane domain (TM) and C-terminal domain (CTD), is responsible for mediating viral fusion and entry.

[0032] Related studies have shown that angiotensin-converting enzyme II (ACE2) is the SARS-CoV-2 cell receptor. In addition, ACE2 is also the receptor of SARS coronavirus; therefore, the way SARS-CoV-2 infects cells should be similar to that of common coronaviruses.

[0033] When common coronaviruses infect cells, target cell proteases activate the S protein by cleaving it into two subunits, S1 and S2. The RBD of the S1 subunit binds to the host cell's receptor, causing a conformational change in the fusion core formed by the HR1 and HR2 domains in the S2 subunit. This exposes the fusion peptide (FP) of the S2 subunit and inserts it into the target cell membrane, triggering membrane fusion and enabling viral entry.

[0034] During the membrane fusion process, the S protein has three main states, including the pre-fusion native state, the pre-hairpin intermediate state, and the stable post-fusion hairpin state.

[0035] Traditional drugs use blocking peptides to prevent cell fusion, but blocking peptides that inhibit viruses have high specificity. Different peptides need to be designed for different viruses. If the main functional segments are not selected, the peptides will be too long, the cost will increase, and the effect will be reduced.

[0036] In order to solve at least one of the above technical problems, the present invention provides a compound having the following structure for use in the preparation of an anti-new coronavirus drug:

[0037] .

[0038] The compounds provided by the present invention can stimulate the host factor ACTN4, inhibit the binding of coronavirus to nsp12, and inhibit the infectious activity of coronavirus. They have low cytotoxicity and high safety. They can be used in the preparation of coronavirus drugs to reduce coronavirus infection and are of great significance for the prevention and treatment of coronavirus.

[0039] As a nucleoside analog, remdesivir exerts its antiviral activity by acting on the viral RNA-dependent RNA polymerase (RdRp) to terminate the replication of viral RNA.

[0040] The compounds of the present invention can target the host factor ACTN4 and activate the host factor ACTN4. ACTN4 inhibits the binding of nsp7 to nsp12 and / or the binding of nsp8 to nsp12, thereby reducing nsp12 binding to the novel coronavirus genome, thereby inhibiting the replication of the novel coronavirus. Therefore, it has inhibitory activity against all viruses that complete the replication of the novel coronavirus through the binding of nsp7 to nsp12 and the binding of nsp8 to nsp12, has good broad-spectrum activity, and plays an important role in the prevention and treatment of coronavirus.

[0041] Therefore, the compound of the present invention has an antiviral mechanism of action different from that of remdesivir, providing a new option for antiviral therapeutic drugs.

[0042] In the present invention, the concentration of higenamine that inhibits cell infection by 50% of the novel coronavirus WT is 5.2 µg / ml, and the concentration of higenamine that inhibits cell infection by 50% of the novel coronavirus BA.5 strain is 5.2 µg / ml, wherein EC50 refers to the half-maximal effect concentration.

[0043] The selectivity index SI of higenamine having the above structure for inhibiting novel coronavirus WT infected cells is 7.26, wherein SI=TOX / AVA, wherein AVA (antiviral activity) refers to EC50, which is 5.2, and TOX (cytotoxicity) refers to CC50, which refers to the concentration at which the drug produces a cytotoxic reaction in 50% of the cells, and is an indicator for measuring the cytotoxicity of the drug, which is 37.73.

[0044] The selectivity index SI of higenamine having the above structure in the present invention for inhibiting cells infected by the new coronavirus BA.5 strain is 67.38, wherein SI=TOX / AVA, wherein AVA (antiviral activity) refers to EC50, which is 0.56, and TOX (cytotoxicity) refers to CC50, which refers to the concentration at which the drug produces a cytotoxic reaction in 50% of the cells, and is an indicator for measuring the cytotoxicity of the drug, which is 37.73.

[0045] The present invention evaluates the inhibitory activity of the compound against novel coronavirus-infected cells by culturing coronavirus.

[0046] In some embodiments, the novel coronavirus is selected from the novel coronavirus wild strain (WT) or the novel coronavirus BA.5 strain.

[0047] The present invention also provides an anti-coronavirus drug, comprising the compound or pharmaceutically acceptable salt of the compound used in the above application, and a pharmaceutically acceptable adjuvant.

[0048] Specifically, "pharmaceutically acceptable" refers to those ligands, materials, compositions, and / or dosage forms that are suitable for administration to a patient within the scope of sound medical judgment and commensurate with a reasonable benefit / risk ratio.

[0049] A "pharmaceutically acceptable carrier" refers to a pharmaceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, or encapsulating material. As used herein, the language "pharmaceutically acceptable carrier" includes buffers, sterile water for injection, solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, that are compatible with drug administration. Each carrier must be "pharmaceutically acceptable" in the sense of being compatible with the other ingredients in the formulation and not harmful to the patient. Suitable examples include, but are not limited to: (1) sugars such as lactose, glucose, and sucrose; (2) starches such as corn starch, potato starch, and substituted or unsubstituted β-cyclodextrins; (3) cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients such as cocoa butter and suppository waxes; (9) oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn starch, and maltose. Rice oil and soybean oil; (10) glycols such as propylene glycol; (11) polyols such as glycerol, sorbitol, mannitol and polyethylene glycol; (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethanol; (20) phosphate buffer; and (21) other nontoxic compatible substances used in pharmaceutical formulations.

[0050] According to different usage modes of the adjuvant, the dosage form of the drug includes at least one of tablets, capsules, aqueous or oily suspensions, granules, emulsions, oral solutions, injections or powders.

[0051] The dosage form and administration mode of the compound of the present invention or its pharmaceutical composition are not particularly limited. For drugs of different dosage forms, a suitable administration mode can be selected for administration.

[0052] Representative routes of administration include, but are not limited to, oral, rectal, parenteral (intravenous, intramuscular or subcutaneous) injection, and topical administration.

[0053] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In these solid dosage forms, the active compound is mixed with at least one conventional inert excipient (or carrier), such as sodium citrate or dicalcium phosphate, or with the following ingredients: (a) fillers or extenders, for example, starches, lactose, sucrose, glucose, mannitol, and silicic acid; (b) binders, for example, hydroxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose, and acacia; (c) humectants, for example, glycerol; (d) disintegrants, for example, agar, calcium carbonate, potato or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate; (e) solubilizers, for example, paraffin; (f) absorption accelerators, for example, quaternary ammonium compounds; (g) wetting agents, for example, cetyl alcohol and glyceryl monostearate; (h) adsorbents, for example, kaolin; and (i) lubricants, for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. In capsules, tablets, and pills, the dosage form may also include a buffer. Solid dosage forms such as tablets, dragees, capsules, pills, and granules may be prepared using coatings and shell materials, such as enteric coatings and other materials known in the art. They may include opacifying agents, and the release of the active compound or compounds in such compositions may be delayed in a certain portion of the digestive tract. Examples of embedding components that may be used are polymeric substances and waxes. If desired, the active compound may also be microencapsulated with one or more of the above-mentioned excipients.

[0054] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, or tinctures. In addition to the active compound, the liquid dosage form may contain inert diluents commonly used in the art, such as water or other solvents, solubilizers, and emulsifiers, specifically ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, propylene glycol, 1,3-butylene glycol, dimethylformamide, and oils, particularly cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil, and sesame oil, or mixtures thereof. In addition to these inert diluents, the composition may also contain adjuvants, such as wetting agents, emulsifiers and suspending agents, sweeteners, flavoring agents, and fragrances. For example, a suspension may contain a suspending agent, specifically ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum methoxide, and agar, or mixtures thereof.

[0055] Compositions for parenteral injection may comprise physiologically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Suitable aqueous or nonaqueous carriers, diluents, solvents or excipients include water, ethanol, polyols and suitable mixtures thereof.

[0056] Dosage forms for topical administration include ointments, powders, patches, sprays and inhalants, which are prepared by mixing the active ingredient with a pharmaceutically acceptable carrier and any preservatives, buffers, or propellants as necessary under sterile conditions.

[0057] The embodiments of the present invention will be described in detail below with reference to examples.

[0058] Example 1

[0059] Third-generation sequencing detection

[0060] The process of third-generation sequencing is as follows Figure 2 As shown: 1 mg of total RNA was extracted from SARS-CoV-2 infected A549-ACE2 and Huh7 cells and purified using an Oligo(dT) kit; RNA sample libraries were then prepared according to the Oxford Nanopore DRS instructions and loaded onto a FLO-MIN106D sequencing chip, followed by a 48-hour sequencing run on a MinION device (Oxford Nanopore Technologies). The specific steps are as follows:

[0061] Messenger RNA (mRNA) purification:

[0062] (1) Take 75 μg of total RNA and dilute to 100 μL with RNase-free H2O in a 1.5 mL nuclease-free EP tube;

[0063] (2) Incubate the 1.5 mL EP tube without nuclease containing 100 μL RNA solution in step (1) at 65°C in a constant temperature metal bath for 2 min to destroy the RNA secondary structure;

[0064] (3) Take 200 μL of 1 mg resuspended Dynabeads magnetic beads and add them to a new 1.5 mL nuclease-free EP tube. After mixing, place the EP tube on a magnetic stand and let it stand for 30 seconds. Discard the supernatant and keep the EP tube.

[0065] (4) Then add 100 μL Binding Buffer to the 1.5 mL nuclease-free EP tube containing magnetic beads, mix and resuspend, and after equilibration of the magnetic beads, place on a magnetic stand and let stand for 30 seconds until the solution is clear. Discard the supernatant and keep the EP tube.

[0066] (5) After adding 100 μL of Binding Buffer to the 1.5 mL nuclease-free EP tube in step (4) to resuspend the magnetic beads, add 100 μL of the solution containing 75 μg of RNA prepared in step (1), mix thoroughly, and incubate the EP tube on a rotary shaker at room temperature for 5 min;

[0067] (6) Place the 1.5 mL EP tube containing the solution and magnetic beads without nuclease from step (5) on a magnetic rack until the solution is clear, discard the supernatant, and keep the EP tube;

[0068] (7) Add 200 μL of Washing Buffer B to the 1.5 mL nuclease-free EP tube in step (6), mix and resuspend, and after equilibration of the magnetic beads, place on a magnetic stand and let stand for 30 s until the solution is clear. Discard the supernatant and repeat step (7) once more, retaining the EP tube.

[0069] (8) Add 10 μL of Elution Buffer to the 1.5 mL nuclease-free EP tube in step (7) and incubate at 65°C in a constant temperature metal bath for 2 min. Immediately place the EP tube on a magnetic rack and let it stand for 30 s until the solution becomes clear.

[0070] (9) Transfer the supernatant from step (8) to a new 1.5 mL nuclease-free EP tube and set aside.

[0071] Library construction:

[0072] (1) In a 0.2 mL PCR tube, add the following components: 3.0 μL NEB Next Quick Ligation Reaction Buffer, 9.0 μL RNA, 0.5 μL RNA CS (RCS), 1.0 μL RT Adapter (RTA), and 1.5 μL T4 DNA Ligase. Incubate at room temperature for 10 min.

[0073] (2) Prepare the following components: 9.0 μL Nuclease-free water, 2.0 μL 10 mmol / L dNTPs, 8.0 μL 5× first-strand buffer, and 4.0 μL 0.1 M DTT. Add the mixture to a 0.2 mL PCR tube and mix well.

[0074] (3) Add 2 μL SuperScript III reverse transcriptase, mix well, incubate at 50°C for 5 min, and then incubate in a thermostatic metal bath at 70°C for 10 min to inactivate the reverse transcriptase;

[0075] (4) Transfer the reverse transcription product to a 1.5 mL EP tube, add 72 μL of resuspended RNA Clean XP beads, mix well, and incubate at room temperature for 5 min;

[0076] (5) Add 150 μL of pre-cooled 70% ethanol, mix thoroughly by inversion, and discard the supernatant;

[0077] (6) Add 20 μL of NF H2O, incubate at room temperature for 5 min, place on a magnetic stand, and transfer the liquid to a new EP tube;

[0078] (7) In a new 1.5 mL Eppendorf DNA LoBind tube, add the following components in sequence: 20.0 μL reverse-transcribed RNA, 8.0 μL NEB Next Quick Ligation Reaction Buffer, 6.0 μL RNA Adapter, 3.0 μL Nuclease-free water, and 3.0 μL T4 DNA Ligase Mix. Incubate at room temperature for 10 min.

[0079] (8) Add 40 μL RNAClean XP beads, mix well, and incubate at room temperature for 5 min;

[0080] (9) Place the EP tube on a magnetic rack and let it stand until the solution is clear. Discard the supernatant, add 150 μL Wash Buffer and wash twice, then discard the supernatant.

[0081] (10) Add 21 μL of Elution Buffer to dissolve the precipitate and incubate at room temperature for 10 min;

[0082] (11) Place the EP tube on a magnetic stand and let it stand until the solution becomes clear. Transfer the liquid to a new 1.5 mL Eppendorf DNA LoBind tube.

[0083] Sample processing: RNA sequencing was performed using Nanppore Direct RNA sequencing (SQK-RNA002).

[0084] Through third-generation sequencing, it was found that there was a downregulated host factor ACTN4 in Huh7 cells (human liver cancer cells, provided by the Wuhan Institute of Virology, Chinese Academy of Sciences) and A549-ACE2 cells (provided by the Wuhan Institute of Virology, Chinese Academy of Sciences), such as Figure 3 shown.

[0085] In Huh7 cells, knockdown constructs (e.g. Figure 3 ) and overexpression (e.g. Figure 4 ) ACTN4 cell line, and then infected with the new coronavirus WT and new coronavirus BA.5 strains respectively. After 48 hours, protein and RNA samples were collected, and Western blot experiments were used to detect changes in viral protein N protein. RT-qPCR was used to detect changes in viral protein N protein and S protein respectively. Figure 3 It can be seen that after knocking down ACTN4, the protein level and RNA level of viral N protein were upregulated, and the RNA level of S protein was also upregulated; Figure 4 It can be seen that after overexpression of ACTN4, the protein level and RNA level of the toxic N protein were downregulated, and the RNA level of the S protein was also downregulated.

[0086] pass Figure 3 and Figure 4 It can be seen that ACTN4 can effectively inhibit the replication of the new coronavirus wild strain WT and the new coronavirus BA.5 strain.

[0087] Example 2

[0088] Cell experiment on the inhibition of novel coronavirus replication by higenamine

[0089] Dimethyl sulfoxide (DMSO) was used to prepare 3 μg / ml, 6 μg / ml, and 18 μg / ml solutions of higenamine (purchased from Selleck), respectively. Huh7 cells were treated with the prepared higenamine at different concentrations and then infected with the new coronavirus WT and the new coronavirus BA.5. Protein and RNA samples were collected 48 hours later. Western blot experiments were used to detect changes in ACTN4 and viral protein N protein, and RT-qPCR was used to detect changes in viral proteins N protein and S protein, respectively.

[0090] from Figure 5 It can be seen that after treatment with different concentrations of higenamine, the protein level of ACTN4 was upregulated, the protein level and RNA level of viral protein N were downregulated, and the RNA level of S protein was also downregulated, indicating that higenamine effectively inhibits the replication of the new coronavirus wild strain WT and the new coronavirus BA.5 strain.

[0091] Example 3

[0092] Animal experiments on the inhibition of novel coronavirus replication by higenamine

[0093] Healthy experimental mice with similar weight were gavaged with the drug one day before, on the day of, and on the second day of infection with the novel coronavirus, and were dissected on the fifth day of infection with the novel coronavirus (experimental process as shown in the figure). Figure 6 ), and the viral load in lung and brain tissues was detected ( Figure 7 and Figure 8 ) and HE staining was used to observe tissue lesions ( Figure 9 ).

[0094] from Figure 7 and Figure 8 It can be seen that higenamine has a better effect of inhibiting viral replication compared with the control group; Figure 9 It can also be seen that compared with the control group, the degree of lesions in the lung tissue and brain tissue treated with higenamine was significantly alleviated.

[0095] It should be understood that the above embodiments are only intended to illustrate the present invention and are not intended to limit the scope of protection of the present invention. In addition, it should be understood that after reading the contents of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

Claims

1. The use of higenamine as the sole active ingredient in the preparation of drugs for the prevention and treatment of the new coronavirus.

2. The use according to claim 1, characterized in that The novel coronavirus includes the novel coronavirus wild strain WT or the novel coronavirus BA.5 strain.

3. The use according to claim 1, characterized in that The drug for preventing and treating the new coronavirus includes the compound or pharmaceutically acceptable salt of the compound used in the above application, and a pharmaceutically acceptable adjuvant.

4. The use according to claim 3, characterized in that The pharmaceutically acceptable adjuvant includes one or more pharmaceutically acceptable carriers, excipients or diluents.

5. The use according to claim 1, characterized in that The dosage form of the drug includes at least one of tablets, capsules, aqueous or oily suspensions, granules, emulsions, oral solutions, injections or powders.

6. The use according to claim 1, characterized in that The administration of the drug includes at least one of oral, intratumoral, rectal, and parenteral injection.

7. The use according to claim 1, characterized in that The concentration of higenamine in the drug for preventing and treating the new coronavirus is ≥0.01wt%.

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