Use of fexofenadine or a pharmaceutically acceptable salt thereof for the preparation of an antiviral medicament

Abstract

The application discloses application of nonsothine or a pharmaceutically acceptable salt thereof in preparation of an antiviral medicine. In vitro medicine experiments and in vivo medicine experiments of the application find that nonsothine or a pharmaceutically acceptable salt, a solvate, a hydrate, a prodrug, an isomer, an analogue, a derivative or a metabolite thereof can significantly inhibit replication of multiple viruses, and especially shows strong antiviral activity in certain virus infection models.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, and in particular relates to the use of fexotinib or its pharmaceutically acceptable salts in the preparation of antiviral drugs. Background Technology

[0002] In recent years, viral infections have become a significant global public health issue, especially with the outbreak of novel viruses posing enormous challenges to the world. Existing antiviral drugs have certain limitations, such as drug resistance, poor treatment efficacy, and significant side effects. Therefore, developing novel antiviral drugs is currently one of the hot topics in medical research. Summary of the Invention

[0003] To address at least some of the technical problems in the prior art, the present invention provides the use of fexotinib or its pharmaceutically acceptable salts, solvates, hydrates, prodrugs, isomers, analogs, derivatives, or metabolites in the preparation of antiviral drugs. Specifically, the present invention includes the following.

[0004] A first aspect of the invention provides the use of fexotinib or a pharmaceutically acceptable salt, solvate, hydrate, prodrug, isomer, analog, derivative or metabolite thereof in the preparation of an antiviral medicament.

[0005] In some embodiments, according to the application described in the present invention, the virus comprises a DNA virus and / or an RNA virus.

[0006] In some embodiments, according to the application described in the present invention, the DNA virus includes at least one of herpes simplex virus, varicella-zoster virus, cytomegalovirus, smallpox virus, monkeypox virus, adenovirus, human papillomavirus, parvovirus, bocavirus, and hepatitis B virus.

[0007] In some embodiments, according to the application described in the present invention, the RNA virus includes at least one of vesicular stomatitis virus, influenza A virus, encephalomyocarditis virus, mouse hepatitis virus, influenza A virus, influenza B virus, influenza C virus, dengue virus, Zika virus, Ebola virus, Marburg virus, Nipah virus, coronavirus, hepatitis A virus, hepatitis C virus, rotavirus, measles virus, human immunodeficiency virus, respiratory syncytial virus, and rabies virus.

[0008] In some embodiments, according to the application described in the present invention, the antiviral treatment includes at least one of the following:

[0009] (1) Inhibit viral invasion of host cells;

[0010] (2) Inhibit viral genome replication;

[0011] (3) Inhibit viral protein processing or assembly;

[0012] (4) Inhibit viral release;

[0013] (5) Reduce the amount or activity of the virus;

[0014] (6) Improve survival rate.

[0015] In some embodiments, according to the application described in the invention, antiviral action is achieved by administering a therapeutically effective amount of the drug to the subject.

[0016] In some embodiments, according to the application described in the invention, the subject includes a mammal.

[0017] In some embodiments, according to the application described in the invention, the mammal includes a human.

[0018] In some embodiments, according to the application described in the invention, the therapeutically effective dose is 0.01-1000 mg / kg.

[0019] A second aspect of the invention provides the use of fexotinib or a pharmaceutically acceptable salt, solvate, hydrate, prodrug, isomer, analog, derivative or metabolite thereof in the preparation of a combination antiviral drug with other drugs.

[0020] This invention, through in vitro and in vivo drug experiments, has found that fexotinib or its pharmaceutically acceptable salts, solvates, hydrates, prodrugs, isomers, analogs, derivatives, or metabolites can significantly inhibit the replication of a variety of viruses, especially exhibiting potent antiviral activity in certain viral infection models. Attached Figure Description

[0021] Figure 1 This study demonstrated that fensoltinib effectively reduced viral load in RAW264.7 cells.

[0022] Figure 2 The results show the effects of non-sotinib antiviral therapy as detected by flow cytometry.

[0023] Figure 3 The effect of nonsotinib on the survival rate of virus-infected mice was shown.

[0024] Figure 4 The study demonstrated the inhibitory effect of fexotinib on viral expression in mouse spleen and liver tissues.

[0025] Figure 5 The study showed that fexotinib inhibited the expression of cytokines in the spleen, liver tissue, and blood of mice. Detailed Implementation

[0026] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0027] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that the upper and lower limits of the range and each intermediate value between them are specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, are also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0028] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0029] application

[0030] One aspect of this invention provides the use of fisogatinib or a pharmaceutically acceptable salt, solvate, hydrate, prodrug, isomer, analog, derivative, or metabolite thereof in the preparation of an antiviral drug. Fisogatinib (also known as BLU-111362, BLU-554) is a small molecule compound developed by Blueprint Medicines Corp., and is a highly effective, selective, orally potent FGFR4 inhibitor (IC50). 50 (5 nM). As an FGFR4 antagonist, it inhibits fibroblast growth factor receptor-4 and exhibits significant antitumor activity in FGFR4-dependent hepatocellular carcinoma models, while also stimulating T cell infiltration into the tumor microenvironment. In oncology, fisogatinib, as a highly selective FGFR4 inhibitor, has been shown to have significant antitumor effects in hepatocellular carcinoma (HCC) models. However, there are currently no reports on its antiviral effects.

[0031] In this invention, the chemical name of Fisogatinib is N-((3S,4S)-3-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)tetrahydro-2H-pyran-4-yl)acrylamide, and its chemical formula is C 24 H 24 C l2 N4O4 has a molecular weight of 503.38, and its molecular structure is shown in formula (I) below:

[0032] (I).

[0033] As used in this article, “pharmaceutically acceptable” means compounds, substances, compositions, and / or dosage forms that are suitable for use in human and animal tissues without excessive toxicity, irritation, allergic reactions, or other problems or complications, within the limits of reasonable medical judgment, and that are commensurate with a reasonable benefit / risk ratio.

[0034] Examples of pharmaceutically acceptable salts of the compounds described herein include those derived from pharmaceutically acceptable inorganic and organic acids and bases. Examples of suitable acid salts include acetates, adipates, benzoates, benzenesulfonates, butyrates, citrates, disaccharides, dodecyl sulfates, formates, fumarates, glycolate, hemisulfates, heptahydrates, hexanoates, hydrochlorides, hydrobromide, hydroiodide, lactates, maleates, malonates, methanesulfonates, 2-naphthalenesulfonates, nicotinates, nitrates, palmitates, phosphates, picrates, neopentanoates, propionates, salicylates, succinates, sulfates, tartrates, toluenesulfonates, and undecanoates. Salts derived from suitable bases include alkali metal (e.g., sodium) salts, alkaline earth metal (e.g., magnesium) salts, ammonium salts, and N-(alkyl)4-(sodium) salts. + Salt.

[0035] As used herein, the term "solvent" refers to an association or complex formed by one or more solvent molecules with the compounds of this invention. Solvents that form solvates include, but are not limited to, water, isopropanol, ethanol, methanol, dimethyl sulfoxide, ethyl acetate, acetic acid, aminoethanol, etc.

[0036] As used herein, the term "hydrate" refers to an associative compound or complex formed with the compounds of this invention when the solvent molecule is water.

[0037] As used herein, the term "isomer" includes enantiomers, diastereomers, and geometric (or conformational) isomers of a given structure. For example, this invention includes R and S configurations for each asymmetry center, Z and E double bond isomers, Z and E conformational isomers, single stereochemical isomers, and mixtures of enantiomers, diastereomers, and geometric (or conformational) isomers. Unless otherwise stated, this invention includes all tautomers of the structure disclosed in fesotinib.

[0038] As used herein, the term "prodrug" refers to a compound that is converted in vivo to the compound shown in formula (I) above. The term "prodrug" also refers to a parent drug molecule that is a pharmacologically inactive derivative capable of spontaneous or enzymatic biotransformation in vivo to release the active drug. Prodrugs are variants or derivatives of the compounds of this invention that have cleavable groups under metabolic conditions. When prodrugs undergo solvent degradation or enzymatic degradation under physiological conditions, they become pharmaceutically active compounds of this invention in vivo. Prodrug forms generally offer advantages in solubility, tissue compatibility, or delayed release in mammalian organisms (see Bundgard, Design of Prodrugs, pp. 7-9, 21-24, Elsevier, Amsterdam 1985 and Silverman, The Organic Chemistry of Drug Design and Drug Action, pp. 352-401, Academic Press, San Diego, CA, 1992).

[0039] As used herein, the term "metabolite" refers to the product obtained in vivo by the metabolism of the aforementioned compound or its salts. A metabolite of a compound can be identified using techniques known in the art, and its activity can be characterized by methods as known in the art. Such products can be obtained by methods such as oxidation, reduction, hydrolysis, acylation, deacylation, esterification, defatting, enzymatic cleavage, etc., of the administered compound.

[0040] In this invention, the term "derivative" refers to a product derived from the substitution of atoms or functional groups in a compound of formula (I) by other atoms or functional groups. The derivatives are not specifically limited to esters, acylates, or metal complexes of compounds of formula (I).

[0041] In this invention, the compounds can be administered as a pharmaceutical composition together with a pharmaceutically acceptable carrier, wherein examples of pharmaceutically acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; (4) powdered tragacanth gum; (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 oil, and soybean oil; (10) Diols, 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) Alginate; (16) Atherless water; (17) Isotonic saline; (18) Ringer's solution; (19) Ethanol; (20) Phosphate buffer solution; (21) Cyclodextrins, such as Captisol ® Targeted ligands attached to nanoparticles, such as Accurins TM (2) and (22) other non-toxic compatible substances used in pharmaceutical formulations, such as polymer-based compositions.

[0042] Examples of pharmaceutically acceptable antioxidants in this invention include: (1) water-soluble antioxidants, such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, sodium sulfite, etc.; (2) oil-soluble antioxidants, such as ascorbate palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, α-tocopherol, etc.; and (3) metal chelating agents, such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, phosphoric acid, etc. Solid dosage forms (e.g., capsules, tablets, pills, sugar-coated pills, powders, granules, etc.) may include one or more pharmaceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and / or any of the following: (1) fillers or extenders, such as starch, lactose, sucrose, glucose, mannitol, and / or silica; (2) binders, such as carboxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose, and / or gum arabic; (3) humectants, such as glycerin. (4) Disintegrants, such as agar, calcium carbonate, potato or cassava starch, alginic acid, certain silicates and sodium carbonate; (5) Solution blockers, such as paraffin; (6) Absorption enhancers, such as quaternary ammonium compounds; (7) Wetting agents, such as cetyl alcohol and glyceryl monostearate; (8) Adsorbents, such as kaolin and bentonite; (9) Lubricants, such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof; and (10) Colorants. Liquid dosage forms may include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, liquid dosage forms may contain inert diluents commonly used in the art (such as water or other solvents), solubilizers and emulsifiers (such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol), oils (such as cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerin, tetrahydrofuran methanol, fatty acid esters of polyethylene glycol and sorbitol, and mixtures thereof.

[0043] In addition to the active compound, the suspension may contain suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and dehydrated sorbitol ester, microcrystalline cellulose, aluminum hydroxide, bentonite, agar and tragacanth gum, and mixtures thereof.

[0044] In addition to the active compound, ointments, pastes, creams and gels may contain excipients such as animal and vegetable fats, oils, waxes, paraffin wax, starch, tragacanth gum, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicic acid, talc and zinc oxide, or mixtures thereof.

[0045] In addition to the active compound, the powders and sprays of this invention may contain excipients such as lactose, talc, silica, aluminum hydroxide, calcium silicate, and polyamide powder, or mixtures thereof. The sprays may also contain conventional propellants (such as chlorofluorocarbons) and volatile unsubstituted hydrocarbons (such as butane and propane).

[0046] In this invention, the formulation can be conveniently presented in a single dosage form and can be prepared by any method well known in the field of pharmaceutics. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will vary depending on the host to be treated and the specific mode of administration. The amount of active ingredient that can be combined with a carrier material to produce a single dosage form will generally be the amount by which the compound produces therapeutic efficacy.

[0047] In this invention, the dosage forms of the compounds of this invention for topical or transdermal application include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches, and inhalants. The active compounds may be mixed under sterile conditions with a pharmaceutically acceptable carrier and with any preservatives, buffers, or propellants that may be required.

[0048] When the compounds disclosed herein are administered to humans or animals as a medicine, they may be given either alone or as a pharmaceutical composition containing, for example, 0.1% to 99.5% (more preferably, 0.5% to 90%) of the active ingredient in combination with a pharmaceutically acceptable carrier.

[0049] In this invention, the preparation can be administered topically, orally, dermally, rectally, vaginally, extragastrically, intranasally, intrapulmonaryly, intraocularly, intravenously, intramuscularly, intraarterially, intrasheathically, intracapsularly, intradermally, intraperitoneally, subcutaneously, subepidermally, or by inhalation.

[0050] Indications

[0051] In this invention, fexotinib or a pharmaceutically acceptable salt thereof can be used to treat viral infections, including DNA viruses and / or RNA viruses. Examples of DNA viruses include, but are not limited to, herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, cytomegalovirus, smallpox virus, monkeypox virus, adenovirus, human papillomavirus, parvovirus, bocavirus, and hepatitis B virus; examples of RNA viruses include, but are not limited to, vesicular stomatitis virus, influenza A virus, encephalomyelitis virus, mouse hepatitis virus, influenza A virus, influenza B virus, influenza C virus, dengue virus, Zika virus, Ebola virus, Marburg virus, Nipah virus, coronavirus, hepatitis A virus, hepatitis C virus, rotavirus, measles virus, human immunodeficiency virus, respiratory syncytial virus, and rabies virus.

[0052] In this invention, "antiviral" refers to improving the condition after viral infection or before or after the onset of functional disorder. This remission or improvement, measured by any standard technique, is at least 5%, 10%, 20%, 40%, 50%, 60%, 80%, 90%, 95%, or 100% compared to an untreated control group under equivalent conditions. Beneficial or desired clinical outcomes include, but are not limited to, the following, whether detectable or undetectable: symptom relief, reduction in disease severity, stabilization of the disease state (i.e., no worsening), delay or slowing of disease progression, improvement or mitigation of the disease state, and reduction (whether partial or complete).

[0053] In a preferred embodiment, the antiviral effects include, but are not limited to, (1) inhibiting viral invasion of host cells; (2) inhibiting viral genome replication; (3) inhibiting viral protein processing or assembly; (4) inhibiting viral release; (5) reducing viral quantity or activity; and (6) increasing survival rate or viability.

[0054] In this invention, the antiviral effect is achieved by administering a therapeutically effective amount of the drug to a subject. Subjects include, but are not limited to, mammals, including but not limited to, humans, mice, rabbits, cats, dogs, cattle, sheep, and pigs.

[0055] The therapeutically effective dose described in this invention refers to a pharmaceutically recognized effective dosage, that is, an amount of the active compound (i.e., fexotinib or its pharmaceutically acceptable salts, solvates, hydrates, prodrugs, isomers, analogs, derivatives or metabolites) sufficient to significantly improve the condition without causing serious side effects. The daily dose of fexotinib or its pharmaceutically acceptable salts, solvates, hydrates, prodrugs, isomers, analogs, derivatives or metabolites is typically 0.01-1000 mg / kg, preferably 0.01-500 mg / kg, or 0.01-400 mg / kg, or 0.01-300 mg / kg, or 0.01-200 mg / kg, or 0.01-150 mg / kg, or 0.01-100 mg / kg, or 0.01-50 mg / kg, or 0.01-40 mg / kg, or 0.01-30 mg / kg, most preferably 0.01-20 mg / kg. Exemplary effective dosages include, for example, 0.01 mg / Kg, 0.05 mg / Kg, 0.1 mg / Kg, 0.2 mg / Kg, 0.3 mg / Kg, 0.4 mg / Kg, 0.5 mg / Kg, 0.75 mg / Kg, 0.95 mg / Kg, 1 mg / Kg, 1.25 mg / Kg, 1.5 mg / Kg, 1.75 mg / Kg, 2 mg / Kg, 2.5 mg / Kg, 2.75 mg / Kg, 3 mg / Kg, 3.25 mg / Kg, 3.5 mg / Kg, 3.75 mg / Kg, 4 mg / Kg, 4.25 mg / Kg, 4.5 mg / Kg, 4.75 mg / Kg, 5 mg / Kg, 5.25 mg / Kg, 5.5 mg / Kg, 5.75 mg / Kg, 6 mg / Kg, and 6.25 mg / Kg. The recommended doses are: 6.5 mg / kg, 6.75 mg / kg, 7 mg / kg, 7.25 mg / kg, 7.5 mg / kg, 7.75 mg / kg, 8 mg / kg, 8.25 mg / kg, 8.5 mg / kg, 8.75 mg / kg, 9 mg / kg, 9.25 mg / kg, 9.5 mg / kg, 9.75 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, and 20 mg / kg. These doses can be administered as a single daily dose, divided into multiple daily doses, or at intervals.

[0056] Combined applications

[0057] One aspect of the present invention provides the use of fexotinib or a pharmaceutically acceptable salt, solvate, hydrate, prodrug, isomer, analog, derivative or metabolite thereof in the preparation of a combination antiviral drug with other drugs.

[0058] In this invention, other drugs include, but are not limited to, remdesivir, ribavirin, favipiravir, acyclovir, valacyclovir, famciclovir, ganciclovir, brivudine, interferon, oseltamivir phosphate, peramivir, zanamivir, mabaloxavir, favipiravir, arbidol, etc.

[0059] Example 1

[0060] The following example illustrates the inhibitory effect of fensoltinib on the virus.

[0061] 1. Experimental Methods

[0062] 1.1 Inhibitory effect of Fisogatinib on viral load in cells

[0063] (1) RAW264.7 cells (2*10) 5 After culturing in 24-well plates for 16 hours, vesicular stomatitis virus (VSV), a non-pathogenic, enveloped, negative-strand RNA rhabdovirus, was added at an MOI of 0.1, followed by the addition of the small molecule compound fisogatinib to a final concentration of 50 nM. After co-culturing for 12 hours, viral load was detected by RT-qPCR. The positive control group consisted of VSV + DMSO, and the negative control group consisted of DMSO. Actb was used as an internal control to calculate relative expression levels.

[0064] (2) RAW264.7 cells (2*10) 5 After culturing in 24-well plates for 16 hours, herpes simplex virus (HSV), a double-stranded linear DNA virus, with an MOI of 0.1 was added, followed by the small molecule compound Fisogatinib, to a final concentration of 50 nM. After co-culturing for 12 hours, viral load was detected by RT-qPCR. The positive control group consisted of HSV + DMSO, and the negative control group consisted of DMSO. Actb was used as an internal control to calculate relative expression values.

[0065] (3) RAW264.7 cells (2*10) 5After culturing in 24-well plates for 16 hours, encephalomyocarditis virus (EMCV), a non-enveloped single-stranded positive-sense RNA virus, with an MOI of 0.1, was added, followed by the small molecule compound fisogatinib, to a final concentration of 50 nM. After co-culturing for 12 hours, viral load was detected by RT-qPCR. The positive control group consisted of EMCV + DMSO, and the negative control group consisted of DMSO. Actb was used as an internal control to calculate relative expression values.

[0066] 1.2 Flow cytometry analysis of the antiviral activity of Fisogatinib

[0067] RAW264.7 cells (2*10) 5 After culturing the cells in 24-well plates for 16 hours, the cells were infected with VSV-GFP at MOI=0.1 for 12 hours. The viral infection and antiviral effects of small molecule drugs were then detected by flow cytometry using the GFP channel.

[0068] 2. Experimental Results

[0069] like Figure 1 As shown, the small molecule compound Fisogatinib can effectively reduce viral load in RAW264.7 cells, significantly inhibit the replication of various DNA or RNA viruses, and exhibits potent antiviral activity.

[0070] like Figure 2 As shown in the flow cytometry results, compared with the control group, the VSV-GFP fluorescence signal in the Fisogatinib-treated experimental group was significantly reduced. The experiment showed that the intracellular viral infection and replication capacity of the Fisogatinib group was reduced, which demonstrated the antiviral efficacy of Fisogatinib.

[0071] Example 2

[0072] The following example illustrates the viral inhibitory effect of fensoltinib in a viral infection model.

[0073] This embodiment conducted experiments in a viral infection model, treating viral-infected mice with Fisogatinib. The results showed that the drug could significantly reduce viral load and improve the survival rate of mice, as detailed below:

[0074] 1. Experimental Methods

[0075] Six-week-old, weight-matched, littermate male C57BL / 6J wild-type mice were selected and housed in a pathogen-free (SPF) facility. Virus solution was diluted with sterile PBS to a final infection dose of 1 × 10⁻⁶ per mouse. 8 Store at 100 μL of PFU in an ice bath at 4°C, avoiding repeated freeze-thaw cycles.

[0076] Mice were randomly assigned to groups, and their initial weight was recorded before the experiment. Mice were gently restrained in a restraint device, and their abdomens were wiped with 75% ethanol to ensure the injection site was uncontaminated. Using a 1 mL insulin syringe (30 G needle), 100 μL of VSV suspension was drawn and slowly injected into the abdominal cavity in the groin area, with the needle inserted to a depth of approximately 3-5 mm to ensure even distribution of the viral suspension and avoid accidental puncture of the intestines or bladder. After injection, the injection site was gently pressed for 5 seconds to prevent extravasation. Following infection, mice were weighed at fixed times daily, and their mental status, activity level, coat condition, and neurological symptoms (such as hind limb paralysis and ataxia) were observed, and survival rates were calculated.

[0077] Blood samples were collected from mice before and one day after infection using the tail vein sampling method. Mice were restrained in a mouse restraint device, and the tail was disinfected with 75% ethanol. After the tail vein was fully dilated, a 28G needle was used to slowly puncture the vein, collecting 100 μL of blood into an EDTA anticoagulant tube. Forty-eight hours post-infection, mice were anesthetized (using intraperitoneal injection of sodium pentobarbital), and spleen and liver tissues were collected under aseptic conditions for subsequent RNA extraction.

[0078] The virus-infected mouse model was divided into a control group and a Fisogatinib treatment group. The changes in their survival rate over time were observed, as well as the expression of viruses and cytokines in the spleen, liver tissue and blood of the mice.

[0079] 2. Experimental Results

[0080] Mouse survival results as follows Figure 3 As shown, the results indicate that fexotinib can effectively inhibit the virus in the viral infection model, thereby greatly improving the survival rate of mice.

[0081] Virus expression in mouse spleen and liver tissues as follows: Figure 4 As shown, the results indicate that fexotinib can effectively inhibit viral expression in the viral infection model.

[0082] The expression of cytokines in the spleen, liver tissue, and blood of mice is as follows: Figure 5 As shown, the results indicate that fexotinib can effectively inhibit the virus in the viral infection model, thereby suppressing the expression of inflammatory cytokines.

[0083] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. These modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. The application of fexotinib in the preparation of antiviral drugs, characterized in that, The virus in question is vesicular stomatitis virus and / or encephalomyocarditis virus.

2. The application according to claim 1, characterized in that, Antiviral effects are achieved by administering a therapeutically effective dose of the aforementioned nonsotinib to the subject.

3. The application according to claim 2, characterized in that, The subjects included mammals.

4. The application according to claim 3, characterized in that, The mammals mentioned include humans.

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