Application of THBS1 inhibitor in preparation of medicine for preventing or treating lung tissue inflammation induced by novel coronavirus

Abstract

The invention discloses an application of a THBS1 inhibitor in preparation of a medicine for preventing or treating lung tissue inflammation induced by novel coronavirus, and provides a related medicine, application and a method, the THBS1 gene inhibitor or a TSP-1 protein inhibitor is used for treating the lung tissue inflammation infected by SARS-CoV-2, the effect is remarkable, and the medicine can be used for preparing medicines for preventing or treating the lung tissue inflammation induced by the novel coronavirus. The SARS-CoV-2 gene is a novel target for treating severe pneumonia caused by SARS-CoV-2 infection.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and particularly relates to the use of an inhibitor of THBS1 in the preparation of a drug for preventing or treating lung tissue inflammation induced by novel coronavirus. Background Art

[0002] The most common symptoms in patients after SARS-CoV-2 infection are fever, chills and sore throat. Most patients show mild symptoms and can recover without hospitalization. However, in some cases, as the disease progresses, patients can present with pneumonia, acute respiratory distress syndrome, organ damage and multiple organ failure, etc., leading to a high risk of death for patients. In addition, the coagulation function in patients after SARS-CoV-2 infection is impaired, which further causes complications related to coagulation and thrombosis.

[0003] TSP1 (thrombospondin) is an adhesive glycoprotein encoded by the THBS1 gene, which can be secreted by various cells into the extracellular matrix and participate in functions such as immune response and coagulation after binding to the corresponding ligands. Summary of the Invention

[0004] To make up for the deficiencies of the prior art, the present invention provides an inhibitor of the THBS1 gene or TSP-1 protein, which treats and alleviates lung tissue inflammation induced by SARS-CoV-2 infection.

[0005] To achieve the above object, the present invention adopts the following technical solutions:

[0006] The present invention provides the use of an inhibitor of the THBS1 gene or TSP-1 protein in the preparation of a drug for treating lung tissue inflammation.

[0007] Furthermore, the inhibitor of the THBS1 gene or TSP-1 protein includes LSKL and its derivatives.

[0008] Furthermore, the lung tissue inflammation is induced by novel coronavirus.

[0009] Furthermore, the drug is administered orally, by suppository, around the lesion, on the surface of the lesion, by topical application, intravenously, parenterally, intraperitoneally, intramuscularly, intralesionally, intrathecally, intranasally or subcutaneously.

[0010] Furthermore, the drug also includes functional excipients.

[0011] Furthermore, the functional excipients include excipients, diluents, dispersion aids, suspension aids, surfactants, isotonic agents, thickeners, emulsifiers, preservatives, lubricants.

[0012] In some embodiments, specific examples of the functional excipients include buffering agents such as phosphates, citrates, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyl dimethyl benzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl esters of p-hydroxybenzoic acid such as methyl or propyl p-hydroxybenzoate; catechol; resorcinol; cyclohexanol; 3-pentanol, and m-cresol); proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrin; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose, or sorbitol; salt-forming counterions such as sodium; metal complexes (e.g., Zn-protein complexes); and / or nonionic surfactants such as TWEEN™, PLURONICS™, or polyethylene glycol (PEG).

[0013] Further, the drug is in the form of a pharmaceutically acceptable salt.

[0014] Further, the pharmaceutically acceptable salt includes an acid addition salt or a base addition salt.

[0015] Further, the acid addition salts include any one or a combination of at least two of hydrochloride, hydrobromide, hydroiodide, phosphate, sulfate, nitrate, ethanesulfonate, toluenesulfonate, benzenesulfonate, acetate, maleate, tartrate, succinate, citrate, benzoate, ascorbate, and salicylate, malonate, adipate, caproate, arginine salt, fumarate, nicotinate, phthalate, or oxalate.

[0016] Further, the base addition salts include lithium salt, sodium salt, potassium salt, barium salt, calcium salt, magnesium salt, aluminum salt, iron salt, ferrous salt, copper salt, zinc salt, or salts formed with morpholine, diethylamine, triethylamine, isopropylamine, trimethylamine, lysine, or histidine.

[0017] In some embodiments, the lung tissue is from a human or non-human mammal. In some embodiments, non-human mammals include birds and non-human mammals such as non-human primates, companion animals (such as dogs and cats), livestock (such as pigs, sheep, cows), and non-domesticated animals such as big cats. The lung tissue in the present invention can be obtained from a human or non-human mammal regardless of which stage of the organism's life cycle it is in.

[0018] As used herein, the term "pharmaceutically acceptable salt" includes conventional salts formed from pharmaceutically acceptable inorganic or organic acids or inorganic or organic bases, as well as quaternary ammonium acid addition salts. More specific examples of suitable acid salts include salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, perchloric acid, fumaric acid, acetic acid, propionic acid, succinic acid, glycolic acid, formic acid, lactic acid, maleic acid, tartaric acid, citric acid, pamoic acid, malonic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, hydroxynaphthoic acid, hydroiodic acid, malic acid, tannic acid, etc. Other acids, such as oxalic acid, although not pharmaceutically acceptable per se, can be used to prepare salts used as intermediates to obtain the compounds of the present invention and their pharmaceutically acceptable salts. More specific examples of suitable base salts include sodium, lithium, potassium, magnesium, aluminum, calcium, zinc, N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, N-methylglucosamine, and procaine salts. Hereafter, when referring to pharmaceutically acceptable salts of salinomycin, it generally means those that can be used in the pharmaceutical field, are harmless to the product or to mammals, or have a reasonable or acceptable benefit / risk ratio.

[0019] The present invention provides the use of an inhibitor of the THBS1 gene or TSP-1 protein in the preparation of a drug for preventing lung tissue inflammation.

[0020] Furthermore, the inhibitor of the THBS1 gene or TSP-1 protein includes LSKL and its derivatives.

[0021] Furthermore, the lung tissue inflammation is induced by the novel coronavirus.

[0022] The present invention provides a drug, which comprises a therapeutically, alleviatingly or prophylactically effective amount of an inhibitor of the THBS1 gene or TSP-1 protein.

[0023] Furthermore, the drug further comprises a second medicament, and the second medicament comprises other drugs for treating inflammation.

[0024] Furthermore, the drugs for treating inflammation include non-steroidal anti-inflammatory drugs, glucocorticoids, antibiotics, antifungals, antivirals, immunosuppressants and biological agents.

[0025] Furthermore, the non-steroidal anti-inflammatory drugs include aspirin, ibuprofen, paracetamol.

[0026] Furthermore, the glucocorticoids include prednisone, dexamethasone, hydrocortisone.

[0027] Furthermore, the antibiotics include penicillins, cephalosporins, quinolones.

[0028] Furthermore, the antifungals include fluconazole, clotrimazole, itraconazole.

[0029] Further, the antiviral agents include acyclovir, ribavirin, and valacyclovir.

[0030] Further, the immunosuppressants and biologics include cyclosporine, dupilumab, and ustekinumab.

[0031] In some embodiments, the antibiotic drugs include cephalosporins, quinolones and fluoroquinolones, penicillins, penicillins / β-lactamase inhibitors, carbapenems, monobactams, macrolides / lincosamines, glycopeptides, rifampicin, oxazolidonones, tetracyclines, aminoglycosides, streptogramins, and sulfonamides.

[0032] In some embodiments, the antiviral drugs include cationic steroid antimicrobials, leupeptin, antipain, amantadine, rimantadine, oseltamivir, zanamivir, ribavirin, or interferon-α2b.

[0033] In some embodiments, the glucocorticoid drugs include prednisone, methylprednisolone, betamethasone, prednisolone, hydrocortisone, cortisone, and dexamethasone.

[0034] In some embodiments, a prophylactically effective amount means an amount of a drug that effectively prevents or substantially reduces the chance of acquiring a disease or disorder, or reduces its severity before acquiring the disease or disorder, or reduces the severity of one or more of its symptoms before the symptoms develop. Generally, prophylactic measures are divided into primary prophylaxis (to prevent disease development) and secondary prophylaxis (where the disease has developed and the patient is protected from worsening of the process). In some embodiments, a therapeutically effective amount means an amount of an active compound or pharmaceutical agent that elicits the biological or medical response sought by a researcher, veterinarian, physician, or other clinician in a tissue, system, animal, or human. The therapeutically or pharmaceutically effective amount of the compound to be administered will be governed by such considerations and will be the minimum amount necessary to ameliorate, cure, or treat a disease or disorder or one or more of its symptoms. The pharmaceutical compositions of the invention will be formulated, administered, and dosed in a manner consistent with good medical practice. Factors considered in this context include the specific disorder being treated, the specific mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site to which the agent is to be delivered, the method of administration, the dosing regimen, and other factors known to the medical practitioner, such as the age, weight, and response of the individual patient.

[0035] The term "treatment" as used in the invention includes injecting or otherwise administering the composition of the invention into a patient, or applying or dosing the composition of the invention to the cells or tissues of a patient, for the purpose of treating, curing, alleviating, mitigating, altering, remedying, improving, enhancing, or affecting the disease or disorder, the symptoms of the disease or disorder, or the risk (or susceptibility) of the disease or disorder. The term "treatment" refers to any sign of success in the treatment or alleviation of an injury, lesion, or disorder, which includes any objective or subjective parameter, such as the alleviation, mitigation, weakening, or making the injury, lesion, or disorder more tolerable to the patient; slowing the rate of degeneration or decline; making the ultimate point of degeneration less debilitating; improving the physical or mental condition of the patient; or, in some cases, preventing the onset of dementia. The treatment or improvement of symptoms can be based on subjective or objective parameters, which include: physical examination, mental assessment, or cognitive tests (such as CDR, MMSE, DAD, ADAS-Cog), or the results of other tests known in the art.

[0036] The term "prevention" as used in the invention refers to preventing the onset, recurrence, or spread of a disease or condition or one or more of its symptoms. In certain embodiments, the term refers to treating or administering a compound provided herein to a patient prior to the appearance of symptoms, specifically to a patient at risk of a disease or condition provided herein. The term encompasses the inhibition or reduction of symptoms of a particular disease. In certain embodiments, specifically, subjects with a family history of the disease are candidates for a prevention regimen. In addition, subjects with a history of recurrent symptoms are also potential candidates for prevention. In this regard, the term "prevention" can be used interchangeably with the term "preventive treatment".

[0037] The term "LSKL" as used in the invention is thrombospondin inhibitor (TSP-1) trifluoroacetate, a tetrapeptide derived from LAP-TGFβ and a competitive TGF-β1 antagonist.

[0038] The invention provides a method for screening drugs for the treatment of lung tissue inflammation in vitro, comprising the following steps: using the THBS1 gene or TSP-1 protein as the drug action target, selecting a TSP-1 protein activity inhibitor or a THBS1 gene expression inhibitor as a candidate primary screening drug; and administering the candidate primary screening drug to in vitro inflammatory lung cells or tissues to screen out drugs with good effects on lung tissue inflammation.

[0039] Further, the lung tissue inflammation is induced by novel coronavirus.

[0040] The invention provides the application of the THBS1 gene or TSP-1 protein in screening drugs for the treatment of lung tissue inflammation, wherein the drugs can inhibit the activity of the TSP-1 protein or inhibit the expression of the THBS1 gene.

[0041] Furthermore, the lung tissue inflammation is induced by novel coronavirus.

[0042] The present invention provides a method for inhibiting lung cell inflammation in vitro, the method comprising using an inhibitor of an effective amount of THBS1 gene or TSP-1 protein.

[0043] Furthermore, the lung tissue inflammation is induced by novel coronavirus.

[0044] Any pharmaceutical composition covered by this application can be orally delivered (for example) via any acceptable and suitable oral formulation. Exemplary oral formulations include (but are not limited to, for example) tablets, troches, lozenges, aqueous and oily suspensions, dispersible powders or granules, emulsions, hard and soft capsules, liquid capsules, syrups, and elixirs. A pharmaceutical composition intended for oral administration can be prepared according to any method known in the art for manufacturing pharmaceutical compositions intended for oral administration.

[0045] Advantages and beneficial effects of the present invention:

[0046] The role played by THBS1 gene or TSP-1 protein in SARS-CoV-2 infection provides new ideas for the discovery of new therapeutic targets for severe cases caused by SARS-CoV-2 infection, and provides strategies for the treatment and prevention of COVID-19. Description of the Drawings

[0047] Figure 1 are the results of lung tissue staining of wild-type mice and Thbs1 - / - mice after infection with SARS-CoV-2.

[0048] Figure 2 are the results of lung tissue staining of wild-type mice and Thbs1 - / - statistics of lung lesions in mice after infection with SARS-CoV-2.

[0049] Figure 3 are the results of lung infection of wild-type mice and TSP-1 inhibitor mice after infection with SARS-CoV-2. Detailed Description of the Invention

[0050] The following further elaborates on this invention in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are presented by way of example and are not intended to limit the present invention. Without departing from the scope of the present invention, the main features of the present invention can be used in various embodiments.

[0051] Example 1

[0052] 1. Experimental materials

[0053] 1.1 Viruses for experiments

[0054] SARS-CoV-2 Delta

[0055] 1.2 Experimental animals and cells

[0056] C57 mice and Thbs1 - / - Mice

[0057] 1.3 Experimental instruments

[0058] Biological safety cabinet (Thermo, USA), pathological section scanner (Hamamatsu, Japan), cell counter (DeNOVIX, USA), centrifuge (Eppendorf, Germany).

[0059] 1.4 Experimental reagents and consumables

[0060] 4% Paraformaldehyde (Biosharp, BL539A), absolute ethanol (Sigma-Aldrich, 64-17-5), xylene (Sigma-Aldrich, 1330-20-7), hematoxylin (Sigma-Aldrich, 517-28-2), 1.5 mL, 2 mL EP tubes (Bioshaip, China).

[0061] 2. Experimental methods

[0062] 2.1 Animal experiments

[0063] The mice were divided into 2 groups: the WT group and the Thbs1 - / - group, and 1×10 5 TCID 50 / 50 μL of the Delta virus strain was used to infect C57 mice and Thbs1 - / - mice (WT group and Thbs1 - / - group, n = 5). After infection, the body weight changes were recorded daily. On 0, 3, and 5 dpi, the lung tissues of the mice were taken for pathological examination to detect the inflammatory characteristics and inflammatory cell infiltration in the lung tissues. All experimental operations related to SARS-CoV-2 virus infection in this study were carried out in an ABSL-3. The animal experiment passed the animal ethics review.

[0064] 2.2 Pathological examination of lung tissues

[0065] 2.2.1 Preparation of paraffin sections of lung tissues

[0066] The collected mouse lung tissues were placed in formalin and fixed overnight. The samples were washed with clear water, and the sections were determined according to the Standard Operating Procedure (SOP) and experimental requirements, and then cut into pieces. Subsequently, the cut pieces were successively placed in 75% alcohol for 30 min, 85% alcohol for 30 min, 90% alcohol for 30 min, 90% alcohol for 30 min, 95% alcohol I for 30 min, 95% alcohol II for 30 min, 100% alcohol I for 30 min, 100% alcohol II for 30 min, and xylene solution for 10 min. Subsequently, dehydration and clearing were carried out, and after completion, they were successively placed in an incubator at 54 °C and 56 °C. After 1 h, the samples were placed in embedding cassettes, and molten paraffin was added for sample embedding.

[0067] 2.2.2 Dewaxing of paraffin sections

[0068] The paraffin sections were successively soaked in xylene I, II, and III for 15 min each, then placed in absolute ethanol I and II for 5 min each, and then placed in 95%, 80%, and 70% ethanol for 2 min each. Finally, they were washed with distilled water until no water droplets adhered to the wall.

[0069] 2.2.3 Hematoxylin-eosin staining

[0070] The sections were placed in hematoxylin, taken out after 5 min, slowly rinsed with tap water for 10 min, and then rinsed with distilled water. Subsequently, the sections were successively added to 70%, 80%, and 95% ethanol, soaked for 2 min, stained with eosin solution for 30 s, and then transferred to 90%, 95%, and 100% ethanol for 1 min each. Finally, they were placed in xylene I, II, and III solutions for 5 min each, and neutral gum was dropped on the tissue sections for sealing.

[0071] 3. Experimental results

[0072] 3.1 After TSP1 knockout, the pulmonary inflammatory characteristics of virus-infected mice can be improved

[0073] At a dose of 1×10 5 TCID 50 wild-type mice and Thbs1 - / - mice were infected, and mouse lung tissues were collected at 0, 3, and 5 dpi respectively, and the inflammation in the lung tissues was detected pathologically. The results were as Figure 1 Compared with Figure 2 shown, the results showed that compared with WT mice, the weight loss of Thbs - / - mice slowed down after infection, and then the weight increased and returned to normal; Thbs - / -After mouse infection, the degree of lung lesions decreased and inflammatory cells decreased. The above results indicate that after knocking out Thbs1, the lung inflammation in virus-infected mice was alleviated.

[0074] Example 2

[0075] 1. Experimental materials

[0076] 1.1 Experimental virus

[0077] SARS-CoV-2 Delta.

[0078] 1.2 Experimental animals and cells

[0079] C57 mice.

[0080] 1.3 Experimental instruments

[0081] Biological safety cabinet (Thermo, USA), pathological section scanning instrument (Hamamatsu, Japan), cell counter (DeNOVIX, USA), centrifuge (Eppendorf, Germany).

[0082] 1.4 Experimental reagents and consumables

[0083] 4% paraformaldehyde (Biosharp, BL539A), absolute ethanol (Sigma-Aldrich, 64-17-5), xylene (Sigma-Aldrich, 1330-20-7), hematoxylin (Sigma-Aldrich, 517-28-2)

[0084] 1.5 mL, 2 mL EP tubes (Bioshaip, China).

[0085] 2. Experimental methods

[0086] 2.1 Animal experiment

[0087] The mice were divided into 2 groups: the WT group and the LSKL inhibitor group. They were respectively infected by intranasal drip with 1×10 5 TCID 50 / 50 μL of the Delta virus strain (n = 5). Lung tissues of the mice were taken at 0, 3, and 5 dpi for pathological detection to detect the inflammatory characteristics and inflammatory cell infiltration in the lung tissues. All experimental operations related to SARS-CoV-2 virus infection in this study were carried out in an ABSL-3. The animal experiment passed the animal ethics review.

[0088] 2.2 Pathological examination of lung tissue

[0089] 2.2.1 Preparation of paraffin sections of lung tissue

[0090] The collected mouse lung tissues were placed in formalin and fixed overnight. The samples were washed with clear water, and the sections were determined according to the Standard Operating Procedure (SOP) and experimental requirements, and then cut into pieces. Subsequently, the cut pieces were successively placed in 75% alcohol for 30 min, 85% alcohol for 30 min, 90% alcohol for 30 min, 90% alcohol for 30 min, 95% alcohol I for 30 min, 95% alcohol II for 30 min, 100% alcohol I for 30 min, 100% alcohol II for 30 min, and xylene solution for 10 min. Subsequently, dehydration and clearing were carried out, and after completion, they were successively placed in incubators at 54 °C and 56 °C. After 1 h, the samples were placed in embedding cassettes, and molten paraffin was added for sample embedding.

[0091] 2.2.2 Deparaffinization of paraffin sections

[0092] The paraffin sections were successively immersed in xylene I, II, and III for 15 min each, then placed in absolute ethanol I and II for 5 min each, and then placed in 95%, 80%, and 70% ethanol for 2 min each. Finally, they were washed with distilled water until water droplets did not hang on the wall.

[0093] 2.2.3 Hematoxylin-eosin staining

[0094] The sections were placed in hematoxylin, taken out after 5 min, slowly rinsed with tap water for 10 min, and then rinsed with distilled water. Subsequently, the sections were successively added to 70%, 80%, and 95% ethanol, immersed for 2 min, stained with eosin solution for 30 s, and then transferred to 90%, 95%, and 100% ethanol for 1 min each. Finally, they were placed in xylene I, II, and III solutions for 5 min each, and neutral gum was dropped on the tissue sections for mounting.

[0095] 3. Experimental results

[0096] 3.1 TSP-1 inhibitor improves the inflammatory characteristics of the lungs of virus-infected mice

[0097] Wild-type mice and inhibitor-group mice were infected with SARS-CoV-2 at a dose of 1×10 5 TCID 50 . Then, wild-type mice were treated with placebo, and inhibitor-group mice were treated with TSP-1 inhibitor. Mouse lung tissues were collected at 0, 3, and 5 dpi respectively, and the inflammation in the lung tissues was detected pathologically. The results are as Figure 3 shown. The results showed that compared with the control-group mice, the degree of lung lesions and the number of inflammatory cells in the LSKL-treated mice were reduced after infection. The above results indicate that the TSP-1 inhibitor can relieve the inflammation of lung tissues induced by COVID-19 infection.

[0098] The description of the above embodiments is only for understanding the method and its core idea of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and modifications can be made to the present invention, and these improvements and modifications will also fall within the protection scope of the claims of the present invention.

Claims

1. Use of an inhibitor of THBS1 gene or TSP-1 protein in the preparation of a drug for treating lung tissue inflammation.

2. The use according to claim 1, wherein the inhibitor of THBS1 gene or TSP-1 protein comprises LSKL and its derivatives; Preferably, the lung tissue inflammation is induced by novel coronavirus.

3. The use according to claim 1, wherein the drug is administered orally, rectally, around the lesion, on the surface of the lesion, topically, intravenously, parenterally, intraperitoneally, intramuscularly, intralesionally, intrathecally, intranasally or subcutaneously; Preferably, the drug further comprises a functional excipient; Preferably, the functional excipient comprises a shaping agent, a diluent, a dispersion aid, a suspension aid, a surfactant, an isotonic agent, a thickening agent, an emulsifier, a preservative, a lubricant; Preferably, the drug is in the form of a pharmaceutically acceptable salt; Preferably, the pharmaceutically acceptable salt comprises an acid addition salt or a base addition salt; Preferably, the acid addition salt comprises any one or a combination of at least two of hydrochloride, hydrobromide, hydroiodide, phosphate, sulfate, nitrate, ethanesulfonate, toluenesulfonate, benzenesulfonate, acetate, maleate, tartrate, succinate, citrate, benzoate, ascorbate and salicylate, malonate, adipate, caproate, arginine salt, fumarate, nicotinate, phthalate or oxalate; Preferably, the base addition salt comprises lithium salt, sodium salt, potassium salt, barium salt, calcium salt, magnesium salt, aluminum salt, iron salt, ferrous salt, copper salt, zinc salt, or a salt formed with morpholine, diethylamine, triethylamine, isopropylamine, trimethylamine, lysine or histidine.

4. Use of an inhibitor of THBS1 gene or TSP-1 protein in the preparation of a drug for preventing lung tissue inflammation.

5. A drug, which comprises a therapeutically, alleviatingly or prophylactically effective amount of an inhibitor of THBS1 gene or TSP-1 protein.

6. The drug according to claim 5, wherein the drug further comprises a second medicament, and the second medicament comprises other drugs for treating inflammation.

7. The drug according to claim 6, wherein the drugs for treating inflammation comprise non-steroidal anti-inflammatory drugs, glucocorticoids, antibiotics, antifungals, antivirals, immunosuppressants and biological agents; Preferably, the non-steroidal anti-inflammatory drugs comprise aspirin, ibuprofen, paracetamol; Preferably, the glucocorticoids comprise prednisone, dexamethasone, hydrocortisone; Preferably, the antibiotics comprise penicillins, cephalosporins, quinolones; Preferably, the antifungals comprise fluconazole, clotrimazole, itraconazole; Preferably, the antivirals comprise acyclovir, ribavirin, valacyclovir; Preferably, the immunosuppressants and biological agents comprise cyclosporine, dupilumab, ustekinumab.

8. A method for in vitro screening of drugs for treating lung tissue inflammation, comprising the following steps: Using THBS1 gene or TSP-1 protein as the drug action target, and selecting a TSP-1 protein activity inhibitor or a THBS1 gene expression inhibitor as a candidate primary screening drug; Administer the candidate drug for primary screening to in vitro inflammatory lung cells or tissues, and screen out the drugs with good effects on lung tissue inflammation; Preferably, the lung tissue inflammation is induced by novel coronavirus.

9. Use of THBS1 gene or TSP-1 protein in screening drugs for treating lung tissue inflammation, wherein the drugs can inhibit the activity of TSP-1 protein or inhibit the expression of THBS1 gene; Preferably, the lung tissue inflammation is induced by novel coronavirus.

10. A method for inhibiting inflammation of lung cells in vitro, the method comprising using an effective amount of an inhibitor of THBS1 gene or TSP-1 protein; Preferably, the lung tissue inflammation is induced by novel coronavirus.

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