Application of a small molecule compound Y020-0023 in anti-SARS-CoV-2 infection

Abstract

The present invention discloses the use of a small molecule compound Y020-0023 in anti-SARS-CoV-2 infection. The present invention creatively discovers for the first time the new drug use of the small molecule compound Y020-0023 in anti-SARS-CoV-2 infection. Experiments in the present invention demonstrate that the small molecule compound Y020-0023 can significantly inhibit SARS-CoV-2 infection without affecting cell viability, and has a good inhibitory effect on SARS-CoV-2 infection. The compound can be used in the development of anti-SARS-CoV-2 infection drugs and has broad application prospects.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technology, and specifically relates to the use of a small molecule compound Y020-0023 in anti-SARS-CoV-2 infection. Background Art

[0002] The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the genus Betavirus in the family Coronaviridae and is a linear, positive-strand RNA virus. Studies have found that SARS-CoV-2 is adjacent to SARS-CoV and SARS-CoV-like groups on the evolutionary tree. The novel coronavirus has four main structural proteins: spike protein (S protein), nucleocapsid protein (N protein), membrane protein (M protein), and envelope protein (E protein). The spike protein is a key structural protein on the surface of SARS-CoV-2 and plays a key role in the virus's infection of host cells. It can bind to the receptor angiotensin-converting enzyme 2 (ACE2) on the host cell surface to mediate viral entry.

[0003] The human diseases caused by coronaviruses are mainly respiratory infections, but they may also cause intestinal infections and neurological symptoms. Human coronavirus was isolated in 1965, but until now, our understanding of it is still quite limited, and the serotype and antigenic variability of coronavirus are still unclear. In addition, coronaviruses can cause repeated infections, indicating that there are multiple serotypes and antigenic variations. There are currently no specific preventive and therapeutic drugs. Only experimental studies have found that azathiouracil, ribavirin, etc. have a significant inhibitory effect on coronaviruses, but the above-mentioned drugs have some adverse reactions after taking them, and with the mutation of the virus and the emergence of new strains, the antiviral effects of these traditional chemical drugs are greatly reduced. Therefore, there is an urgent need to develop new small molecule compounds that are anti-SARS-CoV-2 infection in this field. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a small molecule compound Y020-0023 for use in anti-SARS-CoV-2 infection in the art.

[0005] The present invention adopts the following technical solutions to achieve the above-mentioned invention objectives:

[0006] The first aspect of the present invention provides the use of the small molecule compound Y020-0023 or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form thereof in the preparation of a drug for anti-SARS-CoV-2 infection.

[0007] Furthermore, the structural formula of the small molecule compound Y020-0023 is shown in formula (I):

[0008]

[0009] Formula (I).

[0010] Furthermore, the anti-SARS-CoV-2 infection includes inhibiting SARS-CoV-2 infection and / or preventing SARS-CoV-2 infection.

[0011] Furthermore, the administration dose of the small molecule compound Y020-0023 or its pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form is not less than 0.001 μM.

[0012] Furthermore, the drug comprises a therapeutically and / or prophylactically effective amount of the small molecule compound Y020-0023 or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form thereof.

[0013] Furthermore, the drug further comprises a pharmaceutically acceptable carrier and / or excipient.

[0014] Furthermore, the dosage form of the drug is an oral dosage form, a parenteral dosage form or a topical dosage form.

[0015] Furthermore, the dosage form of the drug is one or more combinations of solutions, tablets, capsules, granules, sustained-release agents, suspensions, dispersants, sprays, emulsions, syrups, and drops.

[0016] In the present invention, the structural formula of the small molecule compound Y020-0023 is shown in formula (I) (as described above in formula (I)), and its corresponding SMILES is N(C(C1C=C2)=O)(C(C=1C=C2)=O)C(C(OC1=CC(C(=C2)C)=C(NC2(C)C)C=C1)=O)C. At present, there has been no research or report related to the anti-SARS-CoV-2 infection of the small molecule compound Y020-0023 described above.

[0017] In the present invention, the full name of SARS-CoV-2 is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It belongs to the Coronaviridae family and the genus Beta coronavirus. SARS-CoV-2 virions are spherical or elliptical, with a diameter of approximately 60-140 nm. Their core is a nucleocapsid composed of single-stranded positive-strand RNA and nucleocapsid protein, surrounded by an envelope inlaid with structural proteins such as the spike protein (S protein), envelope protein (E protein), and membrane protein (M protein). The spike protein plays a key role in the virus's infection of host cells.

[0018] In some embodiments, the inhibition of SARS-CoV-2 infection and / or prevention of SARS-CoV-2 infection includes but is not limited to: inhibiting the invasion of SARS-CoV-2, inhibiting the replication of SARS-CoV-2, or inhibiting the reproduction of SARS-CoV-2, etc.

[0019] In the present invention, the pharmaceutically acceptable salt of the small molecule compound Y020-0023 refers to a pharmaceutically acceptable salt of the small molecule compound Y020-0023, which means those carboxylate salts, amino acid addition salts, etc. of the compound (small molecule compound Y020-0023) of the present invention, which are suitable for contact with patients within the scope of reliable medical judgment, do not produce undue toxicity, irritation, allergic reactions, etc., are commensurate with a reasonable benefit / risk ratio, and are effective for their intended applications, including (if possible) the zwitterionic form of the compound of the present invention.

[0020] For example, the pharmaceutically acceptable salts of the small molecule compound Y020-0023 include, but are not limited to, salts having (as counter ions) alkali metal ions such as Na + 、Li + or K + or salts with alkaline earth metal ions such as Ca 2+ or Mg 2+ or any other pharmaceutically acceptable metal ion such as Zn 2+ or Al 3+ or a pharmaceutically acceptable salt formed with an organic base such as diethanolamine, ethanolamine, N-methylglucamine, triethanolamine or tromethamine.

[0021] In some embodiments, pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali metal and alkaline earth metal hydroxides or organic amines. Examples of metals used as cations include magnesium, potassium, sodium, calcium, and the like. Examples of suitable amines include N,N'-dibenzylethylenediamine, diethanolamine, ethylenediamine, chloroprocaine, choline, N-methylglucamine, and procaine.

[0022] In some embodiments, base addition salts of acidic compounds can be prepared by contacting the free acid form with a sufficient amount of the desired base in a conventional manner to form the salt. The free acid can be regenerated by contacting the salt form with an acid and isolating the free acid in a conventional manner.

[0023] In some embodiments, the salt can be a bisulfite, sulfate, nitrate, phosphate, bisulfate, sulfite, pyrosulfate, pyrophosphate, metaphosphate, bromide, monohydrogenphosphate, dihydrogenphosphate, etc. prepared from an inorganic acid.

[0024] In some embodiments, the salt may also be acetate, maleate, sebacate, octanoate, isobutyrate, malonate, oxalate, propionate, succinate, mandelate, suberate, fumarate, benzoate, or the like prepared from organic acids.

[0025] In some embodiments, pharmaceutically acceptable salts may include cations based on alkali and alkaline earth metals, such as sodium, potassium, calcium, lithium, magnesium, and the like, as well as non-toxic ammonium, quaternary ammonium, and amine cations, including but not limited to ammonium, tetramethylammonium, methylamine, dimethylamine, tetraethylammonium, trimethylamine, triethylamine, ethylamine, and the like. Salts of amino acids, such as gluconate, arginate, galacturonate, and the like are also contemplated.

[0026] In the present invention, a hydrate of the small molecule compound Y020-0023 refers to a compound formed by combining the compound described herein (the small molecule compound Y020-0023) with water. Typically, the hydrate is determined by the ratio of the number of water molecules contained in the hydrate to the number of molecules of the compound in the hydrate. Therefore, a hydrate of a compound can be represented by the general formula R·xH2O, for example, where R is the compound (the small molecule compound Y020-0023) and x is a number greater than 0.

[0027] In the present invention, a solvate of the small molecule compound Y020-0023 refers to a solvent addition form of the compound containing a stoichiometric or non-stoichiometric amount of a solvent, including any solvated form of the compound described herein (the small molecule compound Y020-0023). Conventional solvents include, but are not limited to, water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like. The compounds described herein can be prepared, for example, in crystalline form and can be solvated. Suitable solvates include pharmaceutically acceptable solvates and further include stoichiometric and non-stoichiometric solvates. Representative solvates include hydrates, ethanolates, and methanolates.

[0028] A second aspect of the present invention provides a small molecule compound or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form thereof.

[0029] Furthermore, the small molecule compound is the small molecule compound Y020-0023 described in the first aspect of the present invention.

[0030] A third aspect of the present invention provides any of the following products:

[0031] (1) A pharmaceutical composition comprising a therapeutically and / or prophylactically effective amount of the small molecule compound Y020-0023 described in the first aspect of the present invention or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form thereof;

[0032] (2) A pharmaceutical preparation comprising the pharmaceutical composition;

[0033] Optionally, the pharmaceutical preparation is in the form of an oral dosage form, a parenteral dosage form or a topical dosage form;

[0034] Optionally, the dosage form of the pharmaceutical preparation is one or more combinations of solutions, tablets, capsules, granules, sustained-release agents, suspensions, dispersants, sprays, emulsions, syrups, and drops.

[0035] In some embodiments, the pharmaceutical composition or pharmaceutical preparation can be any pharmaceutically acceptable dosage form, including those suitable for different routes of administration. The dosage form can be conveniently presented in unit dosage form and can be prepared by any method well-known in the pharmaceutical field. These methods include the step of combining the active ingredient with a carrier constituting one or more auxiliary ingredients. Generally speaking, the active ingredient is uniformly and tightly combined with a liquid carrier or a finely divided solid carrier or both, and then, if necessary, the product is molded to prepare the formulation.

[0036] In some embodiments, the preparation of a sustained-release formulation can reduce the frequency of medication use, prolong the duration of drug action, and maintain a stable, effective therapeutic concentration. Compared to conventional tablet formulations, the daily dosage of a sustained-release formulation remains unchanged, but patients can take the drug more conveniently and achieve better compliance. It can also reduce toxic side effects and adverse symptoms caused by rapidly elevated blood drug concentrations, ultimately achieving a better therapeutic effect.

[0037] In some embodiments, in order to prepare the pharmaceutical composition or pharmaceutical preparation of the present invention as described above into tablets, various pharmaceutically acceptable carriers known in the art can be widely used, including diluents, binders, wetting agents, disintegrants, lubricants, and glidants. Diluents can be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.; wetting agents can be water, ethanol, isopropyl alcohol, etc.; adhesives can be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, acacia slurry, gelatin slurry, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinyl pyrrolidone, polyethylene glycol, etc.; disintegrants can be dry starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, sodium bicarbonate and citric acid, polyoxyethylene sorbitan fatty acid ester, sodium lauryl sulfate, etc.; lubricants and glidants can be talc, silicon dioxide, stearate, tartaric acid, liquid paraffin, polyethylene glycol, etc.

[0038] In some embodiments, suitable routes of administration for the small molecule compounds, pharmaceutical compositions, or pharmaceutical formulations described herein include parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural), oral, rectal, nasal, pulmonary, topical (including buccal and sublingual), and the like. It will be appreciated that the preferred route may vary depending on, for example, the condition of the subject. Those skilled in the art may make routine adjustments based on actual circumstances.

[0039] In some embodiments, the effective dose of the small molecule compound, pharmaceutical composition, or pharmaceutical formulation described herein will depend on at least the nature of the condition being treated, toxicity, whether the compound is being used prophylactically (lower doses) or against an active viral infection, the method of delivery, and the pharmaceutical formulation, and will be determined by the clinician using routine dose escalation studies.

[0040] In the present invention, the treatment and / or prevention includes palliative care, which is treatment designed to alleviate symptoms rather than cure a disease, pathological condition, or condition; the term also includes prophylactic treatment, which is treatment intended to minimize or partially or completely inhibit the progression of the relevant disease, pathological condition, or condition; and supportive treatment, which is treatment used to supplement another specific therapy intended to improve the relevant disease, pathological condition, or condition. In a specific embodiment of the present invention, the disease is SARS-CoV-2 infection.

[0041] In the present invention, the therapeutically and / or preventively effective amount includes a therapeutically effective amount and a preventively effective amount.

[0042] The term "therapeutically effective amount" refers to an amount sufficient to provide a therapeutic benefit in the treatment of a disease, disorder, or condition, or to delay or minimize one or more symptoms associated with the disease, disorder, or condition. A therapeutically effective amount of a compound refers to an amount of a therapeutic agent, when used alone or in combination with other therapies, that provides a therapeutic benefit in the treatment of a disease, disorder, or condition. A therapeutically effective amount may include an amount that improves overall treatment, reduces or avoids symptoms or causes of a disease or condition, or enhances the therapeutic effect of other therapeutic agents.

[0043] Herein, the term "prophylactically effective amount" refers to an amount sufficient to prevent a disease, disorder, or condition, or an amount sufficient to prevent one or more symptoms associated with a disease, disorder, or condition, or an amount sufficient to prevent the recurrence of a disease, disorder, or condition. A prophylactically effective amount of a compound refers to an amount of a therapeutic agent, when used alone or in combination with other drugs, that provides a prophylactic benefit in preventing a disease, disorder, or condition. A prophylactically effective amount can include an amount that improves overall prevention or enhances the prophylactic effect of other prophylactic drugs.

[0044] A fourth aspect of the present invention provides an in vitro method for inhibiting SARS-CoV-2 infection for non-therapeutic purposes.

[0045] Furthermore, the method comprises the following steps: treating a system in need with the small molecule compound Y020-0023 described in the first aspect of the present invention or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form thereof.

[0046] In some embodiments, the system comprises a cellular system, a subcellular system, a tissue system, or an organ system.

[0047] In addition, the present invention also provides a method for resisting SARS-CoV-2 infection, or a method for treating and / or preventing SARS-CoV-2 infected subjects, the method comprising the following steps: administering to a subject in need thereof a therapeutically and / or prophylactically effective amount of the small molecule compound Y020-0023 as described above of the present invention or its pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form, pharmaceutical composition or pharmaceutical preparation.

[0048] In the present invention, the subject includes, but is not limited to, humans (i.e., males or females of any age group, e.g., pediatric subjects (e.g., infants, children, adolescents) or adult subjects (e.g., young adults, middle-aged adults, or older adults)) and / or non-human animals, e.g., mammals, e.g., primates (e.g., cynomolgus monkeys, rhesus monkeys), cows, pigs, horses, sheep, goats, rodents, cats, and / or dogs. In some embodiments, the subject is a non-human animal. In some embodiments, the subject is a human.

[0049] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0050] The present invention creatively discovered for the first time a new drug use of the small molecule compound Y020-0023 in anti-SARS-CoV-2 infection. The present invention experimentally proves that the small molecule compound Y020-0023 can significantly inhibit SARS-CoV-2 infection without affecting cell viability, has a good inhibitory effect on SARS-CoV-2 infection, and can be used in the development of anti-SARS-CoV-2 infection drugs. The present invention provides a theoretical basis for the research and development of anti-SARS-CoV-2 infection drugs, provides a new solution for the treatment and / or prevention of SARS-CoV-2 infection, and has important translational significance. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 : Schematic diagram of pseudovirus system construction;

[0052] Figure 2 : Graphs showing the validation results of the constructed system, including: Figure A: Validation results of the constructed 293T cell line overexpressing ACE2; Figure B: Result graph showing that the D614G mutant SARS-CoV-2 pseudovirus has a better infection efficiency;

[0053] Figure 3: Screening results of small molecule compounds with good inhibitory effects on SARS-CoV-2 infection in the compound library. Among them, Figure A: After the preliminary screening of 1,000 small molecules, two drugs with good inhibitory effects were screened out, and their drug IDs are Y020-0023 and G125-0182; Figure B: The corresponding results of drugs Y020-0023 and G125-0182 that can significantly and effectively inhibit SARS-CoV-2 infection;

[0054] Figure 4 : While testing the efficiency of drugs Y020-0023 and G125-0182 in inhibiting SARS-CoV-2 pseudovirus, the corresponding result graphs are also testing the effects of drugs Y020-0023 and G125-0182 on cell viability, among which, Figure A: G125-0182; Figure B: Y020-0023. DETAILED DESCRIPTION

[0055] The present invention will be further described below in conjunction with specific examples. The following specific examples are only used to explain the present invention and are not to be construed as limiting the present invention. Those of ordinary skill in the art will appreciate that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and purpose of the present invention, and that the scope of the present invention is defined by the claims and their equivalents. The reagents and raw materials used in the present invention are readily available to those of ordinary skill in the art and are commercially available unless otherwise specified. The experimental methods for which specific conditions are not specified in the present invention are typically tested under conventional conditions or under conditions recommended by the manufacturer. In particular, the following examples are only used to illustrate the present invention and are not to be construed as limiting the scope of the present invention in any way. It should be noted that the experimental conditions and results described in the following examples are only used to illustrate the present invention and should not and will not limit the present invention described in detail in the claims.

[0056] Experimental verification of the anti-SARS-CoV-2 infection effect of the small molecule compound Y020-0023 in the example

[0057] 1. Experimental Materials

[0058] Plasmids: psPAX2, pCDNA3.1-SARS-CoV-2-spike-Δ19 D614G, pLVX-luc2, pCMV VSVG, pLVX-3×flag-hACE2;

[0059] Cells: 293T;

[0060] Culture medium: DMEM (MACGENE, CM10013);

[0061] Calcium phosphate transfection reagents (MACGENE, CTK001);

[0062] Steady-Glo® Luciferase Assay System (Promega, E2520);

[0063] Mini Scaffold Library (Taoshu Biological, L5600);

[0064] HBSS (MACGENE, CC016).

[0065] 2. Experimental methods

[0066] (1) Construction of SARS-CoV-2 pseudovirus

[0067] 1) Seed cells

[0068] 2.5 × 10 cells were seeded per 10 cm dish. 6 HEK293T cells were cultured for 12 h and virus was encapsulated when the cell density reached about 50%.

[0069] 2) Matching system

[0070] ① Solution A: 3 µg psPAX2 + 3 µg pCDNA3.1-SARS-CoV-2-spike-Δ19 D614 + 6 µg pLVX-luc2 + 1 mL HBS, gently mix 7-8 times, and let stand for 5 minutes;

[0071] ② Slowly add 67 µL of CaCl2 to Solution A, gently mix while adding, gently pipette 7-8 times, and let it stand for 15 minutes;

[0072] ③ Add the system evenly to the culture dish, shake the dish gently from front to back and left to right, and return it to the incubator between viruses.

[0073] 3) Replace the culture medium with fresh one every 6 hours.

[0074] 4) Collect the viral supernatant after 48 h, centrifuge at 800 × g for 5 minutes to remove cell debris, filter through a 0.45 µm filter, and store at -80°C.

[0075] (2) Construction of ACE2 overexpression cell line

[0076] 1) Seed cells

[0077] 2.5 × 10 cells were seeded per 10 cm dish. 6HEK293T cells were cultured for 12 h and virus was encapsulated when the cell density reached about 50%.

[0078] 2) Matching system

[0079] ① Solution B: 5 µg psPAX2 + 5 µg pCMV VSVG + 5 µg pLVX-3×flag-hACE2 + 1 mL HBS, gently mix 7-8 times, and let stand for 5 minutes;

[0080] ② Slowly add 67 µL of CaCl2 to Solution B, gently mix while adding, gently pipette 7-8 times, and let it stand for 15 minutes;

[0081] ③ Add the system evenly to the culture dish, shake the dish gently from front to back and left to right, and return it to the incubator between viruses.

[0082] 3) Replace the culture medium with fresh one every 6 hours.

[0083] 4) Collect viral supernatants at 48 h and 72 h, centrifuge at 800 × g for 5 min to remove cell debris, filter through a 0.45 µm filter, and store at -80°C.

[0084] 5) Virus-infected cells: 1.5×10 cells per 10 cm dish 6 For each HEK293T cell, add 5 mL of DMEM and 5 mL of virus-containing DMEM to the dish and infect for 48 h.

[0085] 6) Screening: Cells were passaged and cultured in DMEM containing puromycin. ACE2 overexpression was detected 4 days after screening.

[0086] 7) Construct 293T cells overexpressing ACE2.

[0087] (3) SARS-CoV-2 pseudovirus infection of cells and detection of infection efficiency

[0088] 1) Dilute the drug to 100 µM: Dispense 2 µL of the 10 mM stock solution into 198 µL of HBSS and pipette to mix.

[0089] 2) Drug pretreatment of cells: Pipette 10 µL of the diluted cells into a black 96-well plate and seed 1.6×10 4 cells / 40µL DMEM in a 96-well plate.

[0090] 3) SARS-CoV-2 pseudovirus infection of cells: After 1 h of drug pretreatment, add 50 µL of DMEM containing SARS-CoV-2 pseudovirus to a black 96-well plate.

[0091] 4) 48 hours after infection, measure the fluorescence reading according to the Steady-Glo instructions.

[0092] 3. Experimental results

[0093] (1) Build system

[0094] Schematic diagram of the construction of the SARS-CoV-2 pseudovirus system Figure 1 As shown, the construction results are as follows Figure 2 As shown, the results showed that the 293T cell line overexpressing ACE2 was successfully constructed ( Figure 2 A), SARS-CoV-2 pseudovirus with D614G mutation has better infection efficiency ( Figure 2 B).

[0095] (2) Screening results

[0096] The compound library used for screening is a molecular scaffold library. Each compound in the library represents a class of compounds with the same scaffold. The 5,033 compounds represent 5,033 different molecular scaffolds. Using the scaffold as a clue, after determining that a particular scaffold structure is effective, the structure can be optimized to extend to more small molecules, thereby identifying "low-toxic, high-efficiency" drugs. Therefore, drug screening based on scaffolds can greatly increase screening efficiency.

[0097] After initially completing the 1000 small molecules ( Figure 3 After screening of A), we screened out two drugs with good inhibitory effects, whose drug IDs are Y020-0023 and G125-0182. Both drugs Y020-0023 and G125-0182 can significantly and effectively inhibit the infection of SARS-CoV-2 (P < 0.05) ( Figure 3 B). The dosage of each drug was 10 μM. All three groups were treated with drugs for 1 h before cells were infected with SARS-CoV-2 pseudovirus and the infection efficiency was measured.

[0098] (3) Drug toxicity testing

[0099] While testing the efficiency of drugs Y020-0023 and G125-0182 in inhibiting SARS-CoV-2 pseudovirus, we also tested the effects of drugs Y020-0023 and G125-0182 on cell viability. The results are as follows: Figure 4As shown in Figures AB, the results show that both drugs Y020-0023 and G125-0182 have a good inhibitory effect on SARS-CoV-2 infection without significantly affecting cell viability. Among them, the concentration gradient of the drug Y020-0023 is 0 μM, 0.25 μM, 0.5 μM, 1 μM, 2 μM, 4 μM, 8 μM, 16 μM, and 32 μM, and the concentration gradient of the drug G125-0182 is 0 μM, 12.5 μM, 25 μM, 50 μM, and 100 μM. The treatment method for both drugs is to pre-treat the cells with the drugs for 1 hour, and then detect the infection efficiency after the cells are infected with SARS-CoV-2 pseudovirus.

Claims

1. Use of the small molecule compound Y020-0023 or a pharmaceutically acceptable salt thereof in the preparation of a drug for anti-SARS-CoV-2 infection, characterized in that: The structural formula of the small molecule compound Y020-0023 is shown in formula (I): Formula (I).

2. The use according to claim 1, characterized in that The anti-SARS-CoV-2 infection includes inhibiting SARS-CoV-2 infection and / or preventing SARS-CoV-2 infection.

3. The use according to claim 1, characterized in that The dosage of the small molecule compound Y020-0023 or a pharmaceutically acceptable salt thereof is not less than 0.001 μM.

4. The use according to claim 1, characterized in that The medicine comprises a therapeutically and / or preventively effective amount of the small molecule compound Y020-0023 or a pharmaceutically acceptable salt thereof.

5. The use according to claim 4, characterized in that The medicament further comprises a pharmaceutically acceptable carrier and / or excipient.

6. The use according to claim 5, characterized in that The dosage form of the drug is an oral dosage form, a parenteral dosage form or a topical dosage form.

7. The use according to claim 1, characterized in that The dosage form of the drug is one or more combinations of solutions, tablets, capsules, granules, sustained-release agents, suspensions, dispersants, sprays, emulsions, syrups, and drops.

8. A method for inhibiting SARS-CoV-2 infection in vitro for non-therapeutic purposes, characterized in that: The method comprises the following steps: treating a system in need thereof with the small molecule compound Y020-0023 or a pharmaceutically acceptable salt thereof as described in claim 1.

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