Application of PPAR family receptor as target spot in preparation of antiviral drugs

Abstract

The invention relates to the technical field of biological medicines, and discloses an application of a PPAR family receptor as a target spot in preparation of an antiviral drug, a PPAR-alpha receptor inhibitor, a PPAR-beta / delta receptor stimulant and / or a PPAR-gamma receptor stimulant are used for activating or inhibiting the PPAR family receptor in cells, the proliferation process of viruses can be disturbed, and the anti-virus effect is improved. According to the present invention, with the application of the compound, the infection of viruses between cells can be weakened, the obvious resistance on the herpes simplex virus type 1 and the varicella-zoster virus can be provided, the anti-infection effect of the partial compound on the viruses is more significant than the anti-infection effect of the positive anti-virus drug ACV, and the good application value can be provided in the broad-spectrum anti-virus field.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to the application of PPAR family receptors as targets in the preparation of antiviral drugs. Background Technology

[0002] The statements in this section provide only background information relevant to the disclosure of this application and may not constitute prior art.

[0003] Viral diseases have always been a major threat to global public health. Antiviral drugs are one of the core weapons to deal with these threats. They can significantly control outbreaks by directly treating and preventing transmission. Given the long development cycle of vaccines, broad-spectrum or specific antiviral drugs are an emergency measure to deal with emerging viral outbreaks and buy valuable time for epidemic prevention and control.

[0004] While antiviral drugs are crucial, their development has long faced a significant limitation: a very limited variety of drugs and targets. This stems primarily from the unique biological characteristics of viruses: they must utilize the host cell's ribosomes, enzyme systems, and other mechanisms for replication. This makes finding an "ideal target" that targets the virus without harming the host cell extremely difficult. Many early drugs were unusable due to poor selectivity and high toxicity. Furthermore, some key viral proteins (such as polymerases) are functionally similar to their host cell counterparts, further increasing the difficulty of developing highly selective inhibitors. Traditional antiviral drugs mainly focus on a few conserved and functionally defined stages in the viral replication cycle. This concentration of targets leads to homogenization of drug structures and technical routes. Once a virus develops resistance to a particular class of drugs, the effectiveness of the entire drug class may be significantly reduced. Combined with the high mutation rate of viruses, which allows for rapid screening of variants insensitive to existing drugs, antiviral drugs urgently need more diverse targets, especially broad-spectrum antiviral strategies based on targeting host factors. For example, targeting host proteins (such as ARF4) could block the replication of various RNA viruses, ensuring effective control of viral infection over a longer period.

[0005] Peroxisome proliferator-activated receptors (PPARs) are members of a nuclear receptor superfamily, comprising three subtypes: PPARα, PPARβ / δ, and PPARγ. As ligand-activated transcription factors, the PPAR family plays a crucial role in the regulation of lipid and glucose metabolism and inflammation; its agonists have been used to treat diseases such as diabetes and hyperlipidemia. Summary of the Invention

[0006] The purpose of this invention is to address the problem of poor target diversity in current antiviral drugs by providing the application of PPAR family receptors as targets in the preparation of antiviral drugs. This solves the problems of lack of antiviral drug targets and high homogeneity, and promotes the development of broad-spectrum antiviral drugs.

[0007] The technical solution of the present invention is as follows: This invention provides, in one aspect, the use of PPAR-α receptor inhibitors in the preparation of drugs for treating herpes simplex virus type 1 infection.

[0008] Another aspect of the present invention provides the use of PPAR-β / δ receptor agonists in the preparation of medicaments against herpes simplex virus type 1 infection.

[0009] Another aspect of the present invention provides the use of PPAR-γ receptor agonists in the preparation of medicaments against herpes simplex virus type 1 infection.

[0010] Another aspect of the present invention provides a pharmaceutical composition for treating herpes simplex virus type 1 infection, comprising a PPAR-α receptor inhibitor, a PPAR-β / δ receptor agonist and / or a PPAR-γ receptor agonist.

[0011] This invention provides, in one aspect, the use of PPAR-α receptor inhibitors in the preparation of drugs for treating varicella-zoster virus infection.

[0012] Another aspect of the present invention provides the use of PPAR-β / δ receptor agonists in the preparation of medicaments for treating varicella-zoster virus infection.

[0013] Another aspect of the present invention provides the use of PPAR-γ receptor agonists in the preparation of medicaments for treating varicella-zoster virus infection.

[0014] Another aspect of the present invention provides a pharmaceutical composition for treating varicella-zoster virus infection, comprising a PPAR-α receptor inhibitor, a PPAR-β / δ receptor agonist, and / or a PPAR-γ receptor agonist.

[0015] Preferably, the PPAR-α receptor inhibitors include GW6471, NXT629, Amezalpat, and MK-886; the PPAR-β / δ receptor agonists include GW0742, Seladelpar, and Lanifibranor (IVA-337); and the PPAR-γ receptor agonists are rosiglitazone, pioglitazone, troglitazone, saroglitazar, glycyrrhizin, tesaglitazar, Wistin, and S26948.

[0016] Another aspect of the present invention provides a target for inhibiting herpes simplex virus type 1 infection, including PPAR-α receptor, PPAR-β / δ receptor and / or PPAR-γ receptor.

[0017] Another aspect of the present invention provides an inhibitory target for varicella-zoster virus infection, including PPAR-α receptor, PPAR-β / δ receptor and / or PPAR-γ receptor.

[0018] Compared with existing technologies, the advantages of this invention are: 1. The application of PPAR family receptors as targets in the preparation of antiviral drugs provides new targets for antiviral infection and effective drug compositions. Cellular anti-infection experiments of related drug compositions have confirmed that PPAR-α receptors, PPAR-β / δ receptors, and / or PPAR-γ receptors can all serve as targets for antiviral infection. Inhibition of PPAR-α receptors by inhibitors, activation of PPAR-β / δ receptors by agonists, and / or activation of PPAR-γ receptors by agonists can significantly enhance the antiviral activity of cells. At the same time, it can induce resistance to a variety of viruses, including herpes simplex virus type 1 and varicella-zoster virus, and has broad-spectrum antiviral activity. Some compounds have antiviral activity exceeding that of the existing positive control drug acyclovir. 2. Application of PPAR family receptors as targets in the preparation of antiviral drugs: Quantitative analysis of viral particle numbers and nucleic acid in infected cell cultures showed that activation or inhibition of PPAR family receptors reduced viral particle release into the supernatant. Quantitative analysis of viral gene expression using quantitative real-time PCR (qPCR) indicated that intervention with host PPAR receptors could inhibit viral genome replication. In summary, targeting host PPAR receptors may inhibit viral infection through multiple mechanisms, including inhibiting replication and release.

[0019] 3. Application of PPAR family receptors as targets in the preparation of antiviral drugs: The drug in this application exerts its antiviral effect by targeting host factors, and has a broad-spectrum antiviral effect, rather than targeting a single strain; at the same time, PPAR family receptors have multiple available targets, which greatly improves the success rate of drug development. Attached Figure Description

[0020] Figure 1 To investigate the anti-HSV-1 infection effect targeting the PPAR family receptor α subtype (PPAR-α), Figure A shows the statistical results of differences in plaque number and total plaque area among the simple infection (VC) group, acyclovir (ACV) group, agonist GW7647 group, and inhibitor GW6471 group; Figure B shows the plaque distribution in culture dishes after crystal violet staining in the VC group, ACV group, GW7647 group, and GW6471 group; Figure C shows the half-maximal inhibitory concentration (IC50) of the PPARα inhibitor GW6471 against HSV-1 viral infection. 50 Measurement results; Figure 2Anti-HSV-1 infection activity targeting the PPAR family receptor β subtype (PPAR-β / δ). Figure A shows the statistical results of differences in plaque number and plaque area among the simple infection (VC) group, acyclovir (ACV) group, inhibitor GSK3787 group, and agonist GW0742 group; Figure B shows the plaque distribution in culture dishes after crystal violet staining in each group. Figure 3 To investigate the anti-HSV-1 infection effect targeting the PPAR family receptor γ subtype (PPAR-γ), Figure A shows the statistical results of differences in plaque size and area among the simple infection (VC) group, acyclovir (ACV) group, the PPAR-γ agonist rosiglitazone (Rg) group, and the PPAR-γ inhibitor T0070907 group; Figure B shows the plaque distribution in culture dishes after crystal violet staining among the VC group, ACV group, Rg group, and T0070907 group; Figure C shows the half-maximal inhibitory concentration (IC50) of Rg against viral infection. 50 Measurement results; Figure 4 To demonstrate the anti-varicella-zoster virus (VZV) activity targeting the α and γ subtypes of the PPAR family receptors, Figure A shows the viral spread in the same field of view within 24–72 hours post-infection in the simple infection group (VZV-GFP), acyclovir group (VZV-GFP+ACV), rosiglitazone Rg group (VZV-GFP+Rg), and GW6471 group (VZV-GFP+GW) (photographed using an inverted fluorescence microscope). Figure B shows the average fluorescence intensity of six randomly selected fields of view 96 hours after viral infection in each group shown in Figure A. Figure 5 To demonstrate the same anti-infective effect using PPAR-γ receptor agonists or inhibitors with different chemical structures, Figure A shows the differences in cell fluorescence and morphology 48 hours after infection in the simple infection group (HSV-1), the PPAR-γ agonist rosiglitazone group (HSV-1+Rg), the PPAR-γ agonist glycyrrhizin group (HSV-1+Glab), and the PPAR-γ inhibitor mifobate group (HSV-1+Mifobate); Figure B shows the degree of infection calculated based on the area of ​​the fluorescent region (photographed using an inverted fluorescence microscope; the experimental cells were fluorescent cell lines constructed by transfecting Vero E6 with the green fluorescent protein gene. The green fluorescent areas in the figure represent cells, and the black background represents empty spots formed after cell infection and lysis). Detailed Implementation

[0021] The specific embodiments listed in this invention are merely examples, and the invention is not limited to the specific embodiments described below. For those skilled in the art, any equivalent modifications and substitutions to the embodiments described below are also within the scope of this invention. Therefore, all equivalent transformations and modifications made without departing from the spirit and scope of this invention should be covered within its scope. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. All reagents or instruments whose manufacturers are not specified are commercially available conventional products. To better illustrate this invention, numerous specific details are provided in the following detailed embodiments. Those skilled in the art should understand that this invention can be practiced even without certain specific details. In other embodiments, methods, means, equipment, and steps well known to those skilled in the art are not described in detail in order to highlight the main points of this invention.

[0022] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art. Unless otherwise specified, all units used in this specification are International Standard Units (SI), and all numerical values ​​and ranges appearing in this invention should be understood to include systematic errors unavoidable in industrial production.

[0023] The features and performance of the present invention will be further described in detail below with reference to embodiments.

[0024] Example 1: Plaque assay to characterize antiherpes simplex virus activity targeting PPAR family receptor α (PPAR-α). A comparison of the activity of the PPAR-α agonist GW7467, the inhibitor GW6471, and the positive control drug acyclovir (ACV) against herpes simplex virus (HSV-1) infection.

[0025] 1. Preparation of Vero E6 monolayer cells: When the cells in a 10 cm culture dish reach 90% confluence, digest the cells with trypsin, then add 2 ml of complete culture medium and gently blow off the cells. After mixing, seed the cells with 150 μL of cell suspension per well of a 12-well plate. Observe after culturing for 24 hours. After the cells grow to form a monolayer, they can be used for subsequent experiments.

[0026] 2. Viral infection: HSV-1 virus stock solution was obtained by infecting HeLa cells and quantified using the plaque assay. The quantified virus stock solution was diluted with serum-free medium to a multiplicity of infection (MOI) of approximately 10. The same volume was then inoculated into each well of a 12-well plate and incubated at 37°C for 1 hour.

[0027] 3. Preparation of drug-containing culture media: Small molecule drugs (such as ACV, GW7467, GW6471) are prepared as stock solutions in advance using DMSO, aliquoted, and stored at -80℃. When using, take out the stock solution, dilute each drug stock solution separately with complete culture medium, prepare drug-containing culture media with a target concentration of 20 µM for ACV, GW7467, and GW6471, and incubate in a water bath until ready for use.

[0028] 4. Prepare the drug-containing cover layer: Weigh 0.5 g of agarose, add 49.5 mL of sterile water, microwave until the agarose is completely dissolved, sterilize with alcohol, transfer to a 50 mL centrifuge tube in a laminar flow hood, replenish the volume lost by evaporation with sterile water, and incubate in a warm water bath until ready for use. Mix the drug-containing culture medium and agarose at a 1:1 ratio to obtain drug-containing cover layers of ACV, GW7467, and GW6471 with a final concentration of 10 µM.

[0029] 5. Post-infection medium change: One hour after viral infection, remove the viral infection medium and wash with PBS 1-2 times. Slowly add 1 mL of the corresponding drug-containing cover layer (agarose-drug-containing medium mixture) to each well, avoiding the formation of air bubbles, and incubate in an incubator for 2-3 days; 6. Crystal violet staining observation: Observe under a microscope on the second and third day after infection. After obvious cytopathic effects appear, discard the covering layer, wash with PBS 1-2 times, add 500 uL of crystal violet staining solution to each well and incubate for 5 min. Wash with PBS once, and then take pictures to count the number and size of plaques in each well.

[0030] The test results are shown in the figure below. Figure 1 A and Figure 1 As shown in B. Figure 1 As shown in Figure A, the inhibitor GW6471 exhibited the same trend of action as the positive control drug acyclovir (ACV), both significantly reducing the number of plaques with marked effects; simultaneously, both the inhibitor GW6471 and the positive control drug acyclovir (ACV) reduced plaque area. Furthermore, the data also indicated that although the number of plaques in the GW6471 group was higher than that in the ACV group, the plaque area was smaller, reflecting a difference in the intervention mechanism; while the number of plaques and the corresponding plaque area increased in the PPAR-α agonist GW7467 group. Figure 1 As shown in B, the number and size of plaques from the inhibitor GW6471 and the positive control drug acyclovir (ACV) were lower than those in the control group; Figure 1 The effects were similar in A, but the number of plaques was higher in the agonist GW7467 than in the control group.

[0031] GW6471 half-inhibition concentration IC50 50 Measurement 1. IC 50The assay was performed using the plaque assay, and the preparation of monolayer cells and the virus infection procedure were the same as steps 1 and 2 above. 2. Prepare drug-containing cover layers with gradient concentrations: Mix complete culture medium with 1% agarose at a 1:1 ratio in advance, dilute GW6471 stock solution with the above mixture, and prepare drug-containing cover layers with concentration gradients of 1 µM, 2.5 µM, 5 µM, 10 µM, and 20 µM. Keep them in a water bath until ready for use.

[0032] The procedures for "changing the solution after infection" and "observation by crystal violet staining" are the same as steps 5 and 6 above. The test results are as follows: Figure 1 As shown in C. Figure 1 As can be seen from C, the IC50 of GW6471 is... 50 It is 5.07 μM.

[0033] In summary, it is evident that the PPAR-α inhibitor GW6471 can enhance the anti-herpes simplex virus activity of cells, with an IC50 value of [missing value]. 50 It is 5.07 μM.

[0034] Example 2: Plaque assay to characterize antiherpes simplex virus activity targeting PPAR family receptor β (PPAR-β / δ). 1. The assay was performed using the plaque assay, and the preparation of monolayer cells and the virus infection procedures were the same as in Example 1 above. Figure 1 Steps 1 and 2 of AB).

[0035] 2. Preparation of drug-containing cover layers: Use complete culture medium to mix with 1% agarose at a 1:1 ratio in advance. Use the above mixed solution to dilute the stock solutions of PPAR-β / δ inhibitor GSK3787 and PPAR-β / δ agonist GW0742 respectively, and prepare drug-containing cover layers of GSK3787 and GW0742 with a final concentration of 5 µM. Keep them in a water bath until ready for use.

[0036] 3. The procedures for "changing the solution after infection" and "observation by crystal violet staining" are the same as described above. Figure 1 Steps 5 and 6 in .AB).

[0037] Test results as follows Figure 2 A and Figure 2 As shown in B. Figure 2 As shown in Figure A, the agonist GW0742 exhibited the same trend of action as the positive control drug acyclovir (ACV), both significantly reducing the number of plaques with marked effects; simultaneously, both GW0742 and ACV also reduced plaque area. However, the number of plaques and the corresponding total plaque area increased in the PPAR-β / δ inhibitor GSK3787 group. Figure 2 As shown in B, the number and size of ACV plaques were lower in the agonist GW0742 compared to the control group; and Figure 2 The effects were similar in A, with no significant difference in the number of plaques observed between the inhibitor GSK3787 and the control group. This indicates that the agonist GW0742 has a significant antibacterial effect.

[0038] Example 3: Plaque assay to characterize antiherpes simplex virus activity targeting PPAR family receptor γ (PPAR-γ) Comparison of the anti-herpes simplex virus activity of the PPAR-γ agonist rosiglitazone (Rg), the inhibitor T0070907, and the positive control drug acyclovir (ACV). 1. The anti-herpes simplex virus activity targeting PPAR-γ was evaluated using the plaque assay, with monolayer cell preparation and virus infection procedures performed as described in Example 1 above. Figure 1 Steps 1 and 2 in AB).

[0039] 2. Preparation of drug-containing cover layers: Use complete culture medium to mix with 1% agarose at a 1:1 ratio in advance. Dilute the Rg, T0070907 and ACV stock solutions separately with the above mixed solution to prepare drug-containing cover layers with a final concentration of 50 µM Rg, 10 µM T00709907 and 10 µM ACV. Keep them in a water bath until ready for use.

[0040] 3. The procedures for "changing the solution after infection" and "observation by crystal violet staining" are the same as in Example 1 above. Figure 1 Steps 5 and 6 in .AB).

[0041] Test results as follows Figure 3 As shown, from Figure 3 As can be seen from A, the PPAR-γ agonist rosiglitazone exhibits the same trend of action as the positive control drug acyclovir, both reducing the number of plaques, and under these conditions, the effect of the Rg group is more significant than that of the ACV group; at the same time, both Rg and ACV also reduce the total area of ​​plaques, and the reduction in the Rg group is also more significant than that in the ACV group; while the PPAR-γ inhibitor T0070907 increases both the number of plaques and the total area of ​​plaques. Figure 3 As can be seen in B, with Figure 3 The effects of A were similar; the number and total area of ​​plaques in Rg and ACV were lower than those in the control group, and under these conditions, the Rg group was more effective than the ACV group; while T0070907 increased the number and area of ​​plaques to some extent.

[0042] Rg half-inhibitory concentration IC50 50 Measurement 1.IC 50 The assay was also performed using the plaque assay, and the preparation of monolayer cells and the virus infection procedures were the same as in Example 1 above. Figure 1 Steps 1 and 2 in AB).

[0043] 2. Prepare drug-containing cover layers with gradient concentrations: Mix complete culture medium with 1% agarose at a 1:1 ratio in advance, and dilute the Rg stock solution separately with the above mixed solution to prepare drug-containing cover layers with concentration gradients of 12.5 µM, 25 µM, 50 µM, 100 µM and 200 µM, and keep them in a water bath until ready for use.

[0044] 3. The procedures for "changing the solution after infection" and "observation by crystal violet staining" are the same as in Example 1 above. Figure 1 Steps 5 and 6 in .AB).

[0045] The results are as follows Figure 3 As shown in C. From Figure 3 As can be seen from C, the half-inhibitory concentration (IC50) of Rg is... 50 The value is 64.78 μM.

[0046] In summary, it is evident that the PPAR-γ agonist Rg (rosiglitazone) can enhance cellular activity against herpes simplex virus, with an IC50 concentration of [missing value]. 50 The value is 64.78 μM.

[0047] Example 4: Characterization of antivaricella-zoster virus activity by fluorescent tagging method for activating PPAR-γ and inhibiting PPAR-α. 1. Prepare ARPE-19 cells: Seed approximately 30-40% ARPE-19 cells in a 10 cm cell culture dish. Once the cells have grown to 90% confluence, prepare for subsequent infection procedures.

[0048] 2. Virus resuscitation: Take one vial of varicella-zoster virus cells that have been cryopreserved at -80°C and are 80% infected (in this example, the virus is preserved by freezing viable cells; after thawing, the cryopreserved cells can be mixed with uninfected cells to infect negative cells), and rapidly thaw them at 37°C. Centrifuge at 500 g for 3 minutes, discard the cryopreservation solution, add fresh DMEM / F12 complete culture medium, and mix well by pipetting.

[0049] 3. After trypsin digestion of the uninfected ARPE-19 cells from step 1 above, the cells were purged with 3 mL of complete culture medium and the cell suspension was collected in a 15 mL sterile centrifuge tube. 300 μL of virus suspension was added to the centrifuge tube and mixed thoroughly. 500 μL of the mixed suspension was then inoculated into each well of a 6-well plate and incubated at 37 ℃ for 12 hours before changing the medium.

[0050] 4. Prepare drug-containing culture medium: Half an hour before changing the medium, dilute the stock solution with DMEM / F12 complete culture medium to prepare a drug-containing culture medium with a final concentration of 10 µM ACV, 50 µM Rg, and 10 µM GW6471, and keep it in a water bath until use.

[0051] 5. Post-infection medium change: 12 hours after infection, remove the original culture medium and wash 1-2 times with PBS. Slowly add 2 mL of the corresponding drug-containing culture medium to each well, avoiding the formation of air bubbles, and continue incubation for 2-3 days. Observe under a microscope at 24h, 48h, and 72h. 6. Observation: The viral infection status was observed and recorded under a microscope at the set time points. Since the strain was pre-tagged with GFP, the green fluorescent cells excited under the microscope were the infected cells. The viral infection status of the same field of view in each group was recorded using a fluorescence inverted microscope equipped with a camera function (24h, 48h, 72h); and at 96 hours, six fields of view were randomly selected from each group of test wells to calculate the average fluorescence intensity for statistical analysis.

[0052] The results are as follows Figure 4 As shown in Figure 4A, compared to the pure virus infection group, the fluorescence intensity of all three drug-treated groups decreased at all time points; simultaneously, under these conditions, the Rg group and GW6471 group showed better results than the positive drug ACV group. Figure 4B shows that the statistical results of the average fluorescence intensity at 96 hours are consistent with... Figure 4 Consistent with conclusion A, both the Rg group and the GW6471 group exhibited anti-varicella-zoster virus activity, with better results than the ACV group.

[0053] Example 5: PPAR-γ receptor agonists or inhibitors with different chemical structures demonstrate similarities to previous experiments ( Figure 3 The same anti-infection results.

[0054] 1. Preparation of Vero E6 (GFP) monolayer cells: When the cells in a 10 cm culture dish reach 90% confluence, trypsin digest the cells, then add 2 mL of complete culture medium and gently blow off the cells. After mixing, seed the cells with 300 μL of cell suspension per well of a 6-well plate. After culturing for 24 hours, observe the cells. Once the cells have grown to form a monolayer, they can be used for subsequent experiments.

[0055] 2. Viral infection: HSV-1 virus stock solution was obtained by infecting HeLa cells and quantified using the plaque assay. The quantified virus stock solution was diluted with serum-free medium to a multiplicity of infection (MOI) of approximately 10. Equal volumes were then inoculated into 6-well plates and incubated at 37 °C for 1 hour.

[0056] 3. Prepare the capping layer: Weigh 0.5 g of agarose, add 49.5 mL of sterile water, microwave until the agarose is completely dissolved, sterilize with alcohol, transfer to a 50 mL centrifuge tube in a laminar flow hood, replenish the volume lost by evaporation with sterile water, and incubate in a warm water bath until ready for use. Mix the drug-containing culture medium with agarose at a 1:1 ratio to obtain a drug-containing capping layer with a final concentration of 50 µM rosiglitazone (Rg), 10 µM PPAR-γ inhibitor mifobate, and 10 µM PPAR-γ agonist glabridin (Glab).

[0057] 4. Change medium after infection: One hour after viral infection, remove the culture medium and wash with PBS 1-2 times. Slowly add 2 mL of the corresponding cover layer (agarose-drug-containing medium mixture) to each well, avoiding the formation of air bubbles, and incubate in an incubator for 2-3 days; 5. Observation: Viral infection status was observed and recorded under a microscope at set time points. Since the cells were pre-transformed with the GFP tag gene, cells exhibiting green fluorescence under the microscope were uninfected cells, while the black background represented empty spots formed by cell lysis after infection. Three fields of view were randomly selected from each experimental well using a fluorescence inverted microscope equipped with a photographing function, and the average fluorescence intensity was calculated for statistical analysis.

[0058] The results are as follows Figure 5 As shown, Figure 5 In Figure A, the PPAR-γ agonist Rg and Glab groups showed more green fluorescence in the field of view, indicating more uninfected cells; while the HSV-1 virus-only infection group and the Mifobate group showed less green fluorescence and more black voids, indicating a higher infection rate; according to Figure 5 The statistical data in B show that the viral infection rate decreased in all three groups, with higher significance in the Rg and Glab groups, especially the Rg group. This indicates that targeting PPAR-γ with other structurally different PPAR-γ agonists also exhibits anti-HSV-1 viral infection activity.

[0059] The embodiments described above merely illustrate specific implementation methods of this application, and while the descriptions are detailed and specific, they should not be construed as limiting the scope of protection of this application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the technical solution of this application, and these modifications and improvements all fall within the scope of protection of this application.

Claims

1. A pharmaceutical composition for treating viral infections, characterized in that, This includes PPAR-α receptor inhibitors, PPAR-β / δ receptor agonists, and / or PPAR-γ receptor agonists.

2. A pharmaceutical composition for treating herpes simplex virus type 1 infection, characterized in that, This includes PPAR-α receptor inhibitors, PPAR-β / δ receptor agonists, and / or PPAR-γ receptor agonists.

3. The pharmaceutical composition for treating herpes simplex virus type 1 infection according to claim 2, characterized in that, The PPAR-α receptor inhibitors include GW6471, NXT629, Amezalpat, and MK-886; the PPAR-β / δ receptor agonists include GW0742, sradpar, and lanilano; and the PPAR-γ receptor agonists are rosiglitazone, pioglitazone, troglitazone, salrogliza, glycyrrhizin, ticagliza, Wistin, and S26948.

4. A pharmaceutical composition for treating varicella-zoster virus infection, characterized in that, This includes PPAR-α receptor inhibitors, PPAR-β / δ receptor agonists, and / or PPAR-γ receptor agonists.

5. The pharmaceutical composition for treating herpes simplex virus type 1 infection according to claim 4, characterized in that, The PPAR-α receptor inhibitors include GW6471, NXT629, Amezalpat, and MK-886; the PPAR-β / δ receptor agonists include GW0742, sradpar, and lanilano; and the PPAR-γ receptor agonists are rosiglitazone, pioglitazone, troglitazone, salrogliza, glycyrrhizin, ticagliza, Wistin, and S26948.

6. Application of PPAR-α receptor inhibitors in the preparation of drugs for antiviral infection.

7. Application of PPAR-β / δ receptor agonists in the preparation of drugs for antiviral infection.

8. Application of PPAR-γ receptor agonists in the preparation of drugs for antiviral infection.

9. A target for inhibiting herpes simplex virus type 1 infection, characterized in that, This includes PPAR-α receptors, PPAR-β / δ receptors, and / or PPAR-γ receptors.

10. A target for inhibiting varicella-zoster virus infection, characterized in that, This includes PPAR-α receptors, PPAR-β / δ receptors, and / or PPAR-γ receptors.

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