Use of pimozide as an inhibitor of African swine fever virus

Abstract

The present invention relates to the use of diphenylpiperidine drugs in preventing or treating African swine fever, specifically the use of pimozide in preventing or treating diseases related to African swine fever and its complications.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, and in particular to the use of a diphenylbutazone substance in treating African swine fever. Background Art

[0002] African swine fever (ASF) is a highly contagious disease caused by the African swine fever virus (ASFV). Highly virulent strains can cause acute mortality in domestic pigs, moderately virulent strains can cause acute to subacute symptoms, and low-virulence strains can cause mild or even subtle symptoms. ASFV was first discovered in Kenya, Africa, in 1921, and then spread to Portugal in Europe in 1957. It then spread to Cuba in South America between 1971 and 1980. Subsequently, outbreaks were reported in other American countries, including Georgia in Asia in 2007 and China in 2018. ASFV has been devastating the global pig industry for a century, and currently no safe and effective vaccine exists. Therefore, the development of anti-ASFV drugs is crucial.

[0003] Pimozide is a dopamine receptor antagonist, D2 receptor antagonist, STAT3 / STAT5 inhibitor, diphenylbutylpiperidine derivative and dopamine antagonist with antipsychotic properties. Pimozide molecular formula: C 18 H 29 F2N3O, relative molecular mass: 461.55. The chemical structure is as follows.

[0004]

[0005] Pimozide selectively inhibits type 2 dopamine receptors in the central nervous system (CNS), thereby inhibiting dopamine neurotransmission and reducing motor and vocal tics and delusions. Pimozide has a high affinity for the α1-adrenoceptor, with a Ki value of 39 nM. Additionally, Pimozide antagonizes α-adrenergic receptors and 5-HT2 receptors. Pimozide has a high affinity for the 5-HT7 receptor (Ki = 0.5 nM). Pimozide reduces STAT5 tyrosine phosphorylation and is used to treat psychiatric disorders and as an antipsychotic. It can also inhibit the proliferation of various cancer cells, such as colorectal cancer, human osteosarcoma, and hepatocellular carcinoma.

[0006] Currently, there are no research reports on the anti-African swine fever virus effect of pimozide, nor are there any related patents published. Summary of the Invention

[0007] In response to the above technical problems, the present application tested the therapeutic effect of the diphenylpiperidine substance pimozide in an in vitro model.

[0008] Specifically, the technical solution of this application is as follows:

[0009] 1. Use of diphenylbutazone-type substances in the preparation of drugs or preparations for preventing or treating African swine fever.

[0010] 2. The use as described in item 1, wherein the diphenylpiperidine substance is one or more of pimozide, fluspiride, fluphenazine and penfluridol.

[0011] 3. The use as described in item 1, wherein the diphenylpiperidine substance is pimozide.

[0012] 4. The use according to item 3, wherein an effective dose of pimozide is administered to the subject, wherein the effective dose is 50 mg / kg to 70 mg / kg

[0013] 5. A composition for preventing or treating African swine fever, comprising a diphenylbutazone substance and pharmaceutically acceptable excipients, and preferably also comprising other pharmaceutically active ingredients.

[0014] 6. The composition according to item 5, wherein the diphenylpiperidine-type substance is one or more of pimozide, fluspiride, fluphenazine and penfluridol.

[0015] 7. The composition according to claim 5, wherein the diphenylpiperidine is pimozide.

[0016] 8. The composition according to item 7, wherein the concentration of pimozide in the composition is 0.625-10 μM.

[0017] 9. The composition according to item 7, wherein the dosage of pimozide is 20 mg / kg-100 mg / kg.

[0018] The advantages of this application are:

[0019] 1. Pimozide has a strong inhibitory effect on ASFV in vitro and has significant anti-ASFV activity at a concentration of 1.19 μM, indicating that it has a highly effective anti-ASFV effect.

[0020] 2. Pimozide has a low cytotoxic effect. The half cytotoxic dose (CC50) in the in vitro cytotoxicity test is 83.75 μM. It shows a low cytotoxic effect when it is more than 40 times higher than the effective concentration. Normal use does not affect the proliferation of PAM cells.

[0021] 3. Pimozide raw materials are widely available, low-cost, safe and reliable, and therefore have great potential value in the development of new drugs for the prevention and treatment of African swine fever. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is a schematic diagram of the CCK-8 method for detecting the cytotoxicity of different concentrations of pimozide on PAM cells.

[0023] Figure 2 Schematic diagram of the effect of different concentrations of pimozide on ASFV proliferation in PAM cells measured by qPCR.

[0024] Figure 3A Schematic diagram of the effect of different concentrations of pimozide on ASFV titer in PAM cells determined by HAD50.

[0025] Figure 3B Schematic diagram of the effect of different concentrations of pimozide on rosette spots formed by ASFV proliferation in PAM cells measured using HAD50.

[0026] Figure 4 Schematic diagram of the effect of different concentrations of pimozide on different proliferation stages of ASFV in PAM cells measured by qPCR. DETAILED DESCRIPTION

[0027] The present application is described in detail below. Although specific embodiments of the present application are shown below, it should be understood that the present application can be implemented in various forms and should not be limited by the embodiments described herein. On the contrary, these embodiments are provided to enable a more thorough understanding of the present application and to fully convey the scope of the present application to those skilled in the art. The scope of protection of the present application shall be determined by the appended claims.

[0028] The present application relates to the use of diphenylbutazone substances in preventing or treating African swine fever.

[0029] As used herein, the term "treat," "treat," or "treating" means to reverse, alleviate, inhibit the progression of, or prevent the disease or condition to which such term applies, or one or more symptoms of such disease or condition.

[0030] The diphenylbutyridines described in this application are a new subtype of the butyrophenone class, formed by replacing the ketone side chain with 4-fluorophenylmethionine. Other drugs in this class include pimozide, fluspirin, fluspirin, and penfluridol. A common feature of this class of drugs is their long duration of action. For example, a single oral dose of pimozide lasts for 24 hours, so a single daily dose is sufficient. Another feature is that they are effective for both acute and chronic schizophrenia, both for positive and negative symptoms. They are both dopamine receptor blockers and calcium ion channel blockers, unlike other antipsychotics, and are therefore unique. This may be responsible for their effectiveness against the negative symptoms of schizophrenia. Systematic research into central calcium ion blockers is reportedly promising a more effective drug for the negative symptoms of schizophrenia.

[0031] The present application also provides the use of diphenylbutazone substances in the preparation of drugs or preparations for preventing or treating African swine fever.

[0032] In some specific embodiments, the African swine fever is an infectious disease caused by the African swine fever virus, preferably an infectious disease caused by the African swine fever virus.

[0033] In some specific embodiments, the African swine fever is selected from the group consisting of high fever, loss of appetite or decreased appetite, systemic convulsions, limb convulsions, fibrous thrombosis, conjunctivitis, depression, conjunctivitis, acute enteritis, purple spots or plaques on the body, bran spots; constipation, diarrhea, vomiting, tremors, drowsiness, fluffy fur, hind limb paralysis, movement disorders, leukopenia, punctate hemorrhages in the kidneys, hemorrhages around lymph node sections; marbled lymph node sections; punctate hemorrhages on the surface of the spleen or wedge-shaped infarct areas on the edges, vascular thrombotic necrosis; punctate hemorrhages in the heart, laryngeal bladder, and gallbladder; leukocytic anemia, decreased white blood cell count, decreased lymphocyte count, and other symptoms.

[0034] In some embodiments, the African swine fever comprises weakness, chills, convulsions, and stunted growth in piglets.

[0035] The present application also provides a composition for preventing or treating African swine fever, which comprises a diphenylbutazone substance and a pharmaceutically acceptable excipient.

[0036] In some specific embodiments, the pharmaceutically acceptable excipients include diluents (e.g., starch, pregelatinized starch, dextrin, sucrose, lactose, mannitol, microcrystalline cellulose, etc.), absorbents (e.g., calcium sulfate, calcium hydrogen phosphate, light magnesium oxide, calcium carbonate, etc.), wetting agents (e.g., water, ethanol, etc.), binders (e.g., hydroxypropyl methylcellulose (HPMC), polyvidone (PVP), starch slurry, syrup, etc.), disintegrants (e.g., dry starch, sodium hydroxymethyl starch, low-substituted hydroxypropyl cellulose, effervescent disintegrants, cross-linked polyvinylpyrrolidone, etc.), lubricants (e.g., magnesium stearate, talc, hydrogenated vegetable oil, polyethylene glycol, micronized silica gel), colorants (e.g., titanium dioxide, sunset yellow, methylene blue, pharmaceutical iron oxide red), coating materials (e.g., acrylic resin, hydroxypropyl methylcellulose, povidone, cellulose acetate, etc.), and the like.

[0037] In a preferred embodiment, the composition further comprises other pharmaceutically active ingredients.

[0038] In some specific embodiments, the other pharmaceutically active ingredients include non-steroidal anti-inflammatory drugs or glucocorticoids, such as aspirin, indomethacin, naproxen, naproxen, diclofenac, rofecoxib, methylprednisolone, beclomethasone dipropionate, prednisolone, hydrocortisone, etc.

[0039] In a specific embodiment, the concentration of the diphenylbutazone in the composition is 0.625-10 μM. For example, it can be 0.625 μM, 0.65 μM, 0.675 μM, 0.7 μM, 0.75 μM, 0.775 μM, 0.8 μM, 0.825 μM, 0.85 μM, 0.875 μM, 0.9 μM, 0.925 μM, 0.95 μM, 0.975 μM, 1 μM, 1.5 μM, 2 μM, 2.5 μM, 3 μM, 3.5 μM, 4 μM, 4.5 μM, 5 μM, 5.5 μM, 6 μM, 6.5 μM, 7 μM, 7.5 μM, 8 μM, 8.5 μM, 9 μM, 9.5 μM, or 10 μM.

[0040] In a specific embodiment, the dosage of the diphenylmethane-based substance is 20 mg / kg-100 mg / kg. For example, the dosage of the diphenylmethane-based substance can be 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, 100 mg / kg, preferably 50 mg / kg-70 mg / kg

[0041] In the present application, the unit of mg / kg refers to the weight of the subject. For example, if the subject weighs 100 kg, 50 mg / kg means that a dose of 50*100 mg of the substance is administered to the subject.

[0042] In a specific embodiment, the medicine or preparation provided herein further includes a pharmaceutically acceptable carrier.

[0043] Specifically, examples of the above-mentioned pharmaceutically acceptable carriers include binders, buffers, antioxidants, solubilizers, thickeners, lubricants, disintegrants, diluents, stabilizers, preservatives, colorants, flavorings, solubility aids, emulsifiers, isotonic agents and the like.

[0044] In a specific embodiment, the drug or preparation provided herein may further include a biodegradable polymer, for example, selected from collagen, chitosan, PLGA, PLA, PGA, PCL or a mixture thereof.

[0045] The medicine or preparation provided in this application can be in the form of tablets, injections, liquid drops, sprays, gels, ointments, powders, lozenges, and any other dosage form acceptable to veterinary clinics.

[0046] In a specific embodiment, the diphenylbutazone substance described in the present application is pimozide.

[0047] In some specific embodiments, the concentration of pimozide in the composition is 0.625-10 μM. For example, it can be 0.625 μM, 0.65 μM, 0.675 μM, 0.7 μM, 0.75 μM, 0.775 μM, 0.8 μM, 0.825 μM, 0.85 μM, 0.875 μM, 0.9 μM, 0.925 μM, 0.95 μM, 0.975 μM, 1 μM, 1.5 μM, 2 μM, 2.5 μM, 3 μM, 3.5 μM, 4 μM, 4.5 μM, 5 μM, 5.5 μM, 6 μM, 6.5 μM, 7 μM, 7.5 μM, 8 μM, 8.5 μM, 9 μM, 9.5 μM, or 10 μM.

[0048] In some specific embodiments, the dosage of pimozide is 20 mg / kg-100 mg / kg. For example, the dosage of pimozide can be 20 mg / kg, 25 mg / kg, 30 mg / kg, 35 mg / kg, 40 mg / kg, 45 mg / kg, 50 mg / kg, 55 mg / kg, 60 mg / kg, 65 mg / kg, 70 mg / kg, 75 mg / kg, 80 mg / kg, 85 mg / kg, 90 mg / kg, 95 mg / kg, 100 mg / kg, preferably 50 mg / kg-70 mg / kg.

[0049] The present application also provides a method for preventing or treating African swine fever, which comprises administering an effective dose of a diphenylbutazone substance or the composition provided in the present application to a subject.

[0050] In a preferred embodiment, the diphenylpiperidine substance is pimozide.

[0051] In a preferred embodiment, the African swine fever is an infectious disease caused by African swine fever virus.

[0052] The effective dose described in this application refers to an amount sufficient to achieve the desired therapeutic result or to affect undesirable symptoms but generally insufficient to cause harmful side effects, and can be easily determined by those skilled in the art. In a specific embodiment, the effective dose is 20 mg / kg-100 mg / kg. In a preferred embodiment, the effective dose is 50 mg / kg-70 mg / kg.

[0053] The methods provided in this application include oral, injection, buccal, inhalation, nasal, rectal, local skin or systemic administration. Specifically, the dosage and administration route to the subject vary according to the symptoms of the disease, the patient's condition, etc., and can be determined by those skilled in the art based on actual conditions.

[0054] In the present application, endocytosis refers to endocytosis, also known as endocytosis, which is the process of transporting extracellular substances into cells through the deformation movement of the plasma membrane.

[0055] The technical method of the present application provides diphenylbutazone substances such as pimozide, which have good viral inhibitory effects. For example, they have significant inhibitory effects on ASFV gene copy number, ASFV titer, ASFV nucleic acid replication and protein synthesis. At the same time, in vitro cytotoxicity tests have found that pimozide has low cytotoxicity, and therefore can be used as a potential drug for the treatment of ASF.

[0056] Example

[0057] This application provides a general and / or specific description of the materials and experimental methods used in the experiments. In the following examples, unless otherwise specified, the reagents or instruments used without indicating the manufacturer are all conventional reagent products that can be obtained commercially.

[0058] The following experiments were conducted with biosafety permits and African swine fever laboratory activity permits:

[0059] The Biosafety Level 3 Laboratory (ABSL-3) of the China Veterinary Drug Administration has obtained a license for research on the pathogen of African swine fever and has registered it, meeting the national biosafety level requirements.

[0060] Unless otherwise specified, the experimental procedures are known in the art. The ASFV used in the following examples is genotype II ASFV (Zuo X, Peng G, Zhao J, et al. Infection of domestic pigs with a genotype II potent strain of ASFV causes cytokine storm and lymphocyte mass reduction. Front Immunol. 2024; 15: 1361531.

[0061] doi:10.3389 / fimmu.2024.1361531).

[0062] Main experimental instruments: constant temperature cell culture incubator, microplate reader.

[0063] Main technical plan: First, the CCK-8 method (Cell Counting Kit-8) was used to detect the toxicity of pimozide on porcine alveolar macrophages (PAM) and determine its safe working concentration. Then, the established ASFV infection model was used to evaluate the protective effect of pimozide on PAM cells infected with ASFV. The evaluation methods mainly included fluorescence quantitative PCR (qPCR) test, half-heterocytic adsorption (HAD) 50 ) tests, tests at different action stages, etc.

[0064] Example 1: Cytotoxicity test of different concentrations of pimozide on PAM cells using CCK-8 method.

[0065] The Cell Counting Kit-8 (CCK-8) is a rapid, highly sensitive, non-radioactive colorimetric assay based on WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitro)-5-(2,4-disulfonylphenyl)-2H-tetrazolium monosodium salt). WST-8 is reduced to a highly water-soluble orange-yellow formazan by mitochondrial dehydrogenases under the action of the electron-coupled carrier 1-MethoxyPMS. The amount of formazan generated is proportional to the number of viable cells, allowing for indirect measurement of viable cell counts and reflecting cell proliferation and cytotoxicity. The absorbance is measured at 450 nm using a microplate reader. Higher absorbance values ​​indicate greater formazan production and a higher number of viable cells. The CCK-8 solution in this kit is a ready-to-use reagent that can be directly added to cell samples and tested after incubation for a certain period of time. There is no need to pre-mix various components.

[0066] Main experimental methods:

[0067] 1.25×10 5 Plate 100 μM PAM per well in a 96-well plate and allow to adhere to the cell wall at 37°C for at least 2 hours. Serial dilutions of pimozide stock solution (10,000 μM) were performed using 1640 containing 9% serum. The dilutions were 2000 μM, 1000 μM, 500 μM, 250 μM, and 125 μM, respectively. Three replicates were performed for each dilution, with 20 μL per well. An additional 80 μL of 1640 containing 9% serum was added to bring the total volume to 200 μL. Final pimozide concentrations were 200 μM, 100 μM, 50 μM, 25 μM, and 12.5 μM. A control group with cells added but no pimozide and a blank group with no cells or pimozide were also established. Incubate at 37°C for 72 hours. Discard the supernatant and add 10 μL of CCK-8 (protected from light) and 90 μL of serum-free 1640 to each well, preventing the presence of bubbles. Incubate the cells at 37°C for 2 hours. 450 Read the OD value of each well. Calculate the results: Cell survival rate = (experimental group - blank group) / (control group - blank group) × 100%.

[0068] The experimental results are as follows Figure 1 The results showed that at a concentration of 50 μM, pimozide had a survival rate of more than 90% for PAM cells and did not affect the proliferation of PAM cells.

[0069] Example 2: qPCR determination of the effect of pimozide on ASFV proliferation in PAM cells.

[0070] Main experimental methods:

[0071] 1.25×10 5 PAM / well was plated on a 96-well plate and allowed to adhere for more than 2 hours. Pimozide was serially diluted using 1640 sera containing 9% serum, with dilutions of 100 μM, 50 μM, 25 μM, 12.5 μM, 6.25 μM, and 0 μM, respectively. 10 μl of PAM cell supernatant was discarded, and each dilution was repeated 3 times. 20 μL of pimozide was added to each well, and 90 μL of ASFV (MOI = 0.16) was added to a total volume of 200 μL. The final drug concentrations were 10 μM, 5 μM, 2.5 μM, 1.25 μM, 0.625 μM, and 0 μM. After standing in a 37°C cell culture incubator for 72 hours, the cells were repeatedly frozen and thawed three times at -80°C. ASFV was collected and nucleic acid was extracted. The number of ASFV copies was detected by qPCR using a p72 primer probe, and the inhibition rate of pimozide on ASFV was calculated.

[0072] Table 1p72 primer names and corresponding sequences

[0073]

[0074] The test results are as follows Figure 2 As shown in the results, the pimozide of the present invention has a significant inhibitory effect on ASFV at concentrations of 0.625 μM to 10 μM, and is dose-dependent.

[0075] Example 3: HAD 50 The effect of pimozide on ASFV titers in PAM cells was determined.

[0076] 1.25×10 5 PAM / well was plated on a 96-well plate and allowed to adhere for more than 2 hours. Pimozide was diluted in 1640 gradients containing 9% serum, with the dilutions being 100μM, 50μM, 25μM, 12.5μM, 6.25μM, and 0μM, respectively. 10μl of PAM cell supernatant was discarded, and each dilution was repeated 3 times, with 20μL of pimozide per well, and 90μL ASFV (MOI=0.16) was added to make a total volume of 200μL. The final drug concentrations were 10μM, 5μM, 2.5μM, 1.25μM, 0.625μM, and 0μM. After standing in a 37°C cell culture incubator for 72h, ASFV was repeatedly frozen and thawed three times at -80°C to collect ASFV. 1.25×10 5 PAM / well was plated in a 96-well plate and allowed to adhere to the wall for more than 2 hours. ASFV treated with each pimozide concentration was diluted 10-fold to 10 -8 , 100 μL per well, add 20 μL of 1% red blood cells at the same time, place in a 37°C cell culture incubator, observe the red blood cell aggregation phenomenon every day for 7 consecutive days. Calculate the half-hemoglobin adsorption dose (HAD) of ASFV50 ), the method is Reed-Muench method.

[0077] like Figure 3A As shown in FIG, the virus titer of the present invention gradually decreases at a concentration of 0.625 μM to 10 μM pimozide. Figure 3B As shown in the figure, the proliferation of African swine fever virus was observed by the number of rosette spots at different pimozide concentrations. As the dose of pimozide increased, the number of rosette spots decreased. Therefore, pimozide has a significant inhibitory effect on the viral titer of ASFV infected PAM cells, and it shows a clear dose-dependent effect.

[0078] Example 4: qPCR determination of the effect of pimozide on different proliferation stages of ASFV in PAM cells.

[0079] 1.25×10 5 Plate 100 μM PAM / well in a 96-well plate and allow to adhere for at least 2 hours. Use 1640 dilutions containing 9% serum to serially dilute pimozide to 50 μM, 25 μM, and 0 μM, respectively. ASFV (MOI = 0.16) was tested. Three replicates were performed for each dilution.

[0080] Direct killing: To investigate the direct killing effect of the drug, 20 μL of each 50 μM, 25 μM, or 0 μM pimozide solution was added to 90 μL of ASFV. The cells were incubated at 37°C for 1 hour and diluted 20-fold to a concentration where pimozide had no inhibitory effect. 10 μL of the PAM cell supernatant was discarded and 110 μL of the diluted solution was added to the PAM cells to a total volume of 200 μL. The cells were incubated in a cell culture incubator for 72 hours.

[0081] Pre-intracellular administration: This is used to investigate drug blocking effects or effects on host factors. Add 20 μL of each of 50 μM, 25 μM, and 0 μM pimozide to PAM cells. Make up the volume to 200 μL with 1640 in 9% serum and incubate at 4°C for 2 hours. Wash the cells three times with 1640. Add 90 μL of ASFV to the PAM cells, add 110 μL of 1640 in 9% serum, and incubate at 4°C for 2 hours. Wash the cells three times with 1640. Add 200 μL of 1640 in 9% serum to the PAM cells and incubate at 37°C for 72 hours.

[0082] During (co-intracellular administration): Discard 10 μL of PAM cell supernatant and add 20 μL each of 50 μM, 25 μM, and 0 μM pimozide and 90 μL of ASFV to PAM cells. Incubate at 37°C for 2 h. Wash with 1640 three times. Add 200 μL of 1640 supplemented with 9% serum to PAM cells and incubate at 37°C for 72 h.

[0083] Post-1 (dosing at 4°C after intracellular entry): Investigate the inhibitory effects of drugs on viral nucleic acid replication and protein synthesis. 90 μL of ASFV was added to PAM cells, then made up to 200 μL with 1640 diluted with 9% serum. Incubate at 4°C for 2 hours and wash three times with 1640 diluted with serum. 20 μL of each of 50 μM, 25 μM, and 0 μM pimozide was added to three groups of PAM cells, then made up to 200 μL with 1640 diluted with 9% serum. Incubate in a cell culture incubator for 72 hours.

[0084] Post-2 (administration after intracellular entry at 37°C): Investigate the inhibitory effects of drugs on viral nucleic acid replication and protein synthesis. 90 μL of ASFV was added to PAM cells, and the volume was then made up to 200 μL with 1640 diluted with 9% serum. The cells were incubated at 37°C for 2 hours and washed three times with 1640 diluted with serum. 20 μL of each of 50 μM, 25 μM, and 0 μM pimozide was added to three groups of PAM cells, and the volume was then made up to 200 μL with 1640 diluted with 9% serum. The cells were incubated in a cell culture for 72 hours.

[0085] After 72 hours of incubation, cells at different stages were frozen and thawed three times at -80°C. ASFV was harvested and nucleic acid was extracted. The ASFV copy number was detected by qPCR using a p72 primer probe, and the differences in ASFV copy number at different stages were compared.

[0086] The test results are as follows Figure 4 As shown, the pimozide of the present invention has no direct killing effect on ASFV. The copy number of the p72 gene is significantly reduced one day and two days after treatment, indicating that pimozide plays an inhibitory role in the nucleic acid replication and protein synthesis stages of the virus.

[0087] The foregoing merely illustrates the principles of the present application. It should be understood that the scope of the present application is not intended to be limited to the exemplary aspects described herein, but rather includes all currently known and future developed equivalents. In addition, it should be noted that, without departing from the technical principles of the present application, several improvements and modifications may be made, and such improvements and modifications shall also be considered within the scope of the present application.

Claims

1. Use of diphenylbutazone substances in the preparation of drugs for preventing or treating African swine fever; wherein, The diphenylbutazone substance is pimozide.

2. The method of claim 1, wherein an effective dose of pimozide is administered to a subject, wherein the effective dose is 50 mg / kg to 70 mg / kg.

Images