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

Abstract

The invention discloses an application of a small molecule compound Y020-0023 in resisting SARS-CoV-2 infection, the new application of the small molecule compound Y020-0023 in resisting SARS-CoV-2 infection is creatively found for the first time, and experiments prove that the small molecule compound Y020-0023 can be used for preparing a medicine for resisting SARS-CoV-2 infection under the condition that the cell activity is not influenced, so that the application of the small molecule compound Y020-0023 in resisting SARS-CoV-2 infection is realized, and the application of the small molecule compound Y020-0023 in resisting SARS-CoV-2 infection is realized. According to the present invention, the SARS-CoV-2 infection inhibition effect is provided, the SARS-CoV-2 infection can be significantly inhibited, the good inhibition effect on the SARS-CoV-2 infection can be provided, and the application prospect is broad.

Description

Technical Field

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

[0002] The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belongs to the betavirus genus of the Coronaviridae family 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 in the evolutionary tree. The new coronavirus has four main structural proteins: spike protein (S protein), nucleocapsid protein (N protein), membrane protein (M protein), and envelope protein (E protein). Among them, the spike protein is an important structural protein on the surface of the SARS-CoV-2 virus and plays a key role in the process of the virus infecting host cells. It can bind to the receptor angiotensin-converting enzyme 2 (ACE2) on the surface of the host cell to mediate the virus's entry into the cell.

[0003] The human diseases caused by coronavirus are mainly respiratory infections, but they may also cause intestinal infections and neurological symptoms. Human coronavirus was isolated in 1965, but its understanding is still quite limited, and the serotype and antigenic variability of coronavirus are still unclear. In addition, coronavirus can be repeatedly infected, indicating that there are multiple serotypes and antigenic variations. There are currently no specific preventive and therapeutic drugs. Only in experimental studies have it been found that azathiouracil, ribavirin, etc. have a significant inhibitory effect on coronavirus, 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 resist 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 its pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form 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 dosage 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 preventively 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 also contains 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 as shown in formula (I) (as described above in formula (I)), and the 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 is no research or report related to the small molecule compound Y020-0023 described above and anti-SARS-CoV-2 infection.

[0017] In the present invention, the full name of SARS-CoV-2 is severe acute respiratory syndrome coronavirus 2, referred to as SARS-CoV-2. It belongs to the Coronaviridae family and the genus Beta coronavirus. SARS-CoV-2 virus particles are spherical or elliptical, with a diameter of about 60-140 nm. Its core is a nucleocapsid composed of single-stranded positive-strand RNA and nucleocapsid protein, which is wrapped with an envelope on the outside, and the envelope is inlaid with structural proteins such as spike protein (S protein), envelope protein (E protein) and membrane protein (M protein). Among them, the spike protein plays a key role in the process of virus 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 the pharmaceutically acceptable salt of the small molecule compound Y020-0023, which means those carboxylates, 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) zwitterionic forms of the compounds of the present invention.

[0020] For example, the pharmaceutically acceptable salts of the small molecule compound Y020-0023 include, but are not limited to, alkali metal ions (as counter 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 metals and alkaline earth metal hydroxides or organic amines. Examples of metals used as cations are magnesium, potassium, sodium, calcium, etc. Examples of suitable amines are N, N'-dibenzylethylenediamine, diethanolamine, ethylenediamine, chloroprocaine, choline, N-methylglucamine, 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 in a conventional manner and isolating the free acid.

[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, etc., prepared from organic acids.

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

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

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

[0028] The 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] The 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 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, dispersions, 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 components. Generally speaking, the active ingredient is uniformly and closely 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 sustained-release preparations can reduce the number of medications, prolong the duration of drug action, and maintain a stable effective therapeutic concentration. Compared with ordinary tablet specifications, the daily dosage of sustained-release preparations has not changed, but patients can take medicine more conveniently and have better compliance. At the same time, it can reduce toxic and side effects, reduce adverse symptoms caused by rapid increases in blood drug concentrations, and achieve better therapeutic effects.

[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. The diluent may be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.; the wetting agent may be water, ethanol, isopropanol, etc.; the adhesive may be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, acacia gum slurry, gelatin slurry, sodium carboxymethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinyl pyrrolidone, polyethylene glycol, etc.; the disintegrant may 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 dodecyl sulfate, etc.; the lubricant and glidant may be talc, silicon dioxide, stearate, tartaric acid, liquid paraffin, polyethylene glycol, etc.

[0038] In some embodiments, suitable routes of administration of the small molecule compounds, pharmaceutical compositions or pharmaceutical preparations of the present invention include parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural), oral, rectal, nasal, pulmonary, topical (including oral and sublingual), etc. It is understood that the preferred route may vary, for example, according to the condition of the subject. Those skilled in the art may make routine adjustments according to actual conditions.

[0039] In some embodiments, the effective dose of the small molecule compound, pharmaceutical composition or pharmaceutical formulation described herein will depend at least on 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 treatment, i.e. treatment designed to relieve symptoms rather than cure a disease, pathological state or condition; the term also includes preventive treatment, i.e. treatment aimed at minimizing or partially or completely inhibiting the development of the relevant disease, pathological state or condition; and supportive treatment, i.e. treatment used to supplement another specific therapy aimed at improving the relevant disease, pathological state or condition. In a specific embodiment of the present invention, the disease refers to a SARS-CoV-2 infection disease.

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

[0042] Wherein, the therapeutically effective amount refers to an amount sufficient to provide a therapeutic benefit in the process of treating a disease, disorder or condition, or an amount that delays or minimizes one or more symptoms associated with the disease, disorder or condition. The therapeutically effective amount of a compound refers to the amount of a therapeutic agent when used alone or in combination with other therapies, which provides a therapeutic benefit in the process of treating 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] Wherein, the preventive 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 to prevent the recurrence of a disease, disorder or condition. The preventive effective amount of a compound refers to the amount of a therapeutic agent when used alone or in combination with other drugs, which provides a preventive benefit in the process of preventing a disease, disorder or condition. The preventive effective amount may include an amount that improves overall prevention, or an amount that enhances the preventive effect of other preventive 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 or its pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form described in the first aspect of the present invention.

[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 a therapeutically and / or preventively effective amount of the small molecule compound Y020-0023 as described above or its pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form, pharmaceutical composition or pharmaceutical preparation of the present invention to a subject in need.

[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 discovers for the first time a new drug use of the small molecule compound Y020-0023 in anti-SARS-CoV-2 infection. The present invention proves through experiments that the small molecule compound Y020-0023 can significantly inhibit the infection of SARS-CoV-2 without affecting cell viability, has a good inhibitory effect on the infection of SARS-CoV-2, 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 transformational significance. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0052] Figure 2 : Result diagram of system verification, where A: Result diagram of verification of the constructed 293T cell line overexpressing ACE2; B: Result diagram corresponding to the good infection efficiency of the D614G mutated SARS-CoV-2 pseudovirus;

[0053] Figure 3: Screening results of small molecule compounds with good inhibitory effects on SARS-CoV-2 infection in the compound library, where A: After the preliminary screening of 1,000 small molecules, two drugs with good inhibitory effects were screened, and their drug IDs are Y020-0023 and G125-0182; 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 of the effects of drugs Y020-0023 and G125-0182 on cell viability are tested, where Figure A: G125-0182; Figure B: Y020-0023. DETAILED DESCRIPTION

[0055] The present invention is further described below in conjunction with specific examples. The following specific examples are only used to explain the present invention and cannot be construed as limiting the present invention. It can be understood by those of ordinary skill in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and purposes of the present invention, and 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 easily available to those of ordinary skill in the art, and can be obtained from commercial sources unless otherwise specified. The experimental methods for which specific conditions are not specified in the present invention are usually 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 should not limit 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 small molecule compound Y020-0023 against SARS-CoV-2 infection

[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 Biology, 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 6 HEK293T cells were cultured for 12 h, and virus was ready 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, mix gently 7-8 times, and let stand for 5 min;

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

[0072] ③ Add the system evenly into the culture dish, gently shake the dish back and forth and left and right to evenly mix, 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 min 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 6HEK293T cells were cultured for 12 h and virus was ready 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 min;

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

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

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

[0083] 4) Collect the viral supernatant 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 DMEM containing virus to the dish and infect for 48 h.

[0085] 6) Screening: Cells were passaged and cultured in DMEM containing puromycin; the overexpression effect of ACE2 was detected after 4 days of 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: Add 2 µL of 10 mM stock solution to 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 into a black 96-well plate.

[0091] 4) 48 h after infection, detect 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 skeleton library. Each compound in the library represents a class of compounds with the same skeleton as it. The 5033 compounds represent 5033 molecular skeletons. With the skeleton as a clue, after determining that a certain skeleton structure plays a role, the structure can be optimized to extend more small molecules and find "low-toxic and high-efficiency" drugs. Therefore, screening drugs by skeleton can greatly increase the efficiency of screening.

[0097] After initially completing the 1000 small molecules ( Figure 3 A) After screening, we screened out two drugs with good inhibitory effects, whose drug IDs are Y020-0023 and G125-0182. The 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 group was 10 μM. The treatment methods of the three groups were that the cells were pretreated with drugs for 1 h, and the infection efficiency was detected after the cells were infected with SARS-CoV-2 pseudovirus.

[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 AB, the results show that drugs Y020-0023 and G125-0182 have good inhibitory effects on SARS-CoV-2 infection without significantly affecting cell viability. Among them, the concentration gradient of drug Y020-0023 is 0 μM, 0.25 μM, 0.5 μM, 1 μM, 2 μM, 4 μM, 8 μM, 16μM, 32 μM, and the concentration gradient of drug G125-0182 is 0 μM, 12.5 μM, 25 μM, 50 μM, 100 μM. The treatment method of both drugs is to pre-treat cells with drugs for 1 h, and the infection efficiency is detected after the cells are infected with SARS-CoV-2 pseudovirus.

Claims

1. Use of a 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, 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 its pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form is not less than 0.001 μM.

4. The use according to claim 1, characterized in that: The medicament comprises a therapeutically and / or preventively effective amount of the small molecule compound Y020-0023 or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form 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 small molecule compound or a pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form thereof, characterized in that: The small molecule compound is the small molecule compound Y020-0023 described in claim 1.

9. Any of the following products: (1) A pharmaceutical composition, characterized in that: The pharmaceutical composition 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 as described in claim 1; (2) A pharmaceutical preparation, characterized in that the pharmaceutical preparation comprises the pharmaceutical composition; Optionally, the pharmaceutical preparation is in an oral dosage form, a parenteral dosage form or a topical dosage form; Optionally, the dosage form of the pharmaceutical preparation is one or more combinations of solutions, tablets, capsules, granules, sustained-release agents, suspensions, dispersions, sprays, emulsions, syrups, and drops.

10. 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 with the small molecule compound Y020-0023 or its pharmaceutically acceptable salt, hydrate, enantiomer, diastereomer, solvate or crystalline form as described in claim 1.

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