Interference peptide for inhibiting interaction of interferon gene stimulating factors and application thereof

Abstract

The invention relates to an interference peptide for inhibiting interaction of interferon gene stimulating factors and application of the interference peptide, and belongs to the technical field of biological medicines. The invention designs and synthesizes an interference peptide of a targeted interferon gene stimulating factor, and particularly, the interference peptide is designed as a disulfide bond forming site region of the targeted interferon gene stimulating factor, so that the interaction of the interferon gene stimulating factor can be specifically destroyed; therefore, excessive activation of downstream signals caused by high polymerization of interferon gene stimulating factors can be avoided. The interference peptide disclosed by the invention is combined with an acting surface of a dimerization structural domain mediating oligomerization of the interferon gene stimulating factor to destroy disulfide bond mediated intermolecular interaction, so that excessive activation of the interferon gene stimulating factor caused by virus infection is inhibited, and the purpose of relieving organ injury caused by excessive generation of inflammatory factors in cells is achieved; therefore, effective treatment of clinical virus infection is realized.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technologies, and particularly to an interfering peptide that inhibits the interaction of stimulator of interferon genes and its application. Background Art

[0002] Stimulator of interferon genes (STING protein), as a key regulatory factor in the body's immune response, plays a core role in maintaining the body's immune balance. When the body encounters a viral infection, for example, when herpes virus invades, the double-stranded DNA of the virus will be recognized by relevant receptors in the cell, and then the STING protein is activated. After the STING protein is activated, through a series of cascade reactions, it recruits and activates serine-threonine protein kinase (TBK1 protein kinase). Subsequently, the TBK1 protein kinase phosphorylates interferon regulatory factor 3 (IRF3). The phosphorylated IRF3 dimerizes and translocates into the nucleus to initiate the transcription of cytokines such as type I interferon, thereby triggering the body's antiviral immune response. In an inflammatory state, such as in sterile inflammation caused by tissue damage, abnormal metabolites or damage-associated molecular patterns in the cell can also activate the STING protein, triggering a similar immune-inflammatory cascade reaction.

[0003] However, the strong stimulation of the virus can also lead to overactivation of the STING protein, thus breaking the body's immune balance and triggering an excessive inflammatory response. In dengue virus infection, due to the strong stimulation of the virus on the immune system, the STING protein is overactivated, resulting in the continuous and massive release of a large number of inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), etc., triggering a cytokine storm, leading to symptoms such as severe vascular leakage and organ dysfunction in patients, significantly increasing the risk of patient death. In autoimmune inflammatory diseases such as systemic lupus erythematosus, nucleic acid substances produced by the body itself abnormally activate the STING protein, and the continuous overactivation causes the inflammatory response to spread throughout multiple organ systems of the body, resulting in extensive tissue damage, such as proteinuria in the case of kidney involvement and pain and deformity caused by joint inflammation.

[0004] Currently, for the inflammatory response caused by the overactivation of STING protein, clinical intervention measures are very limited. Traditional immunosuppressants, such as glucocorticoids, although can inhibit the overall immune response to a certain extent, but due to the lack of specificity of their action, while inhibiting the excessive inflammatory response, they also severely inhibit the normal immune defense function of the body, resulting in patients being prone to various infectious diseases, and long-term use will also cause various serious side effects such as osteoporosis and abnormal blood sugar. And some monoclonal antibody drugs targeting inflammatory factors under development, although can block the action of specific inflammatory factors, but due to the complexity of the inflammatory response, the blockade of a single inflammatory factor often cannot effectively control the cascade inflammatory response caused by the overactivation of STING protein, and the treatment effect is not satisfactory. Therefore, it is urgent to develop an intervention measure that can accurately target the overactivation of STING protein, effectively inhibit the excessive inflammatory response and have less side effects. Summary of the Invention

[0005] To this end, the technical problem to be solved by the present invention is to overcome the problem in the prior art that there is a lack of an intervention measure that can accurately target the overactivation of STING protein, effectively inhibit the excessive inflammatory response and have less side effects.

[0006] To solve the above technical problem, the present invention provides an interfering peptide that inhibits the interaction of stimulator of interferon genes and its application. Based on the basic function of STING protein and the mechanism of its overactivation leading to immune inflammatory damage of the body, the present invention artificially designs and synthesizes an interfering peptide targeting STING protein. This interfering peptide binds to the binding surface of the dimer domain that mediates the oligomerization of STING protein, destroys the intermolecular interaction mediated by disulfide bonds, and then inhibits the overactivation of STING protein caused by virus infection, achieving the purpose of alleviating organ damage caused by the excessive production of cellular inflammatory factors, thereby realizing the effective treatment of clinical diseases.

[0007] The first object of the present invention is to provide an interfering peptide that inhibits the interaction of STING protein, and the amino acid sequence of the interfering peptide is as shown in SEQ ID NO.1.

[0008] Further, the interfering peptide is a D-amino acid reverse isomer. D-amino acids are degraded more slowly in animals than natural L-amino acids. Modifying the interfering peptide into a D-amino acid reverse isomer can endow the interfering peptide with good tolerance and therapeutic effect.

[0009] Further, the interfering peptide inhibits the oligomerization of STING protein.

[0010] The second object of the present invention is to provide an application of the above interfering peptide in the preparation of drugs for preventing or treating virus infection.

[0011] Further, the virus includes severe acute respiratory syndrome coronavirus 2.

[0012] Further, the drug for preventing or treating virus infection alleviates the inflammatory damage caused by virus infection. The inflammatory damage includes, but is not limited to, alveolar septum thickening, hemagglutination, and inflammatory cell infiltration.

[0013] The third object of the present invention is to provide a drug for inhibiting hemagglutination, and the drug includes the above-mentioned interfering peptide. The interfering peptide binds to stimulator of interferon genes, inhibits the increase in the expression of coagulation factor III caused by the overactivation of stimulator of interferon genes, and thus inhibits hemagglutination.

[0014] The fourth object of the present invention is to provide a drug for inhibiting serine-threonine protein kinase phosphorylation, and the drug includes the above-mentioned interfering peptide. The interfering peptide inhibits the phosphorylation of serine-threonine protein kinase by stimulator of interferon genes by inhibiting the interaction of stimulator of interferon genes.

[0015] The fifth object of the present invention is to provide an immunosuppressive composition, and the immunosuppressive composition includes the above-mentioned interfering peptide.

[0016] The sixth object of the present invention is to provide an application of the above-mentioned interfering peptide in the preparation of a STING protein inhibitor.

[0017] Further, the STING protein inhibitor inhibits the oligomerization of STING protein.

[0018] Further, the STING protein inhibitor inhibits the interaction between STING protein and serine-threonine protein kinase.

[0019] The seventh object of the present invention is to provide a drug for inhibiting the interaction of stimulator of interferon genes, and the drug includes the above-mentioned interfering peptide.

[0020] The eighth object of the present invention is to provide an application of the above-mentioned interfering peptide in the preparation of an anti-inflammatory product, and the anti-inflammatory product inhibits the generation of inflammatory factors, wherein the inflammatory factors are selected from one or more of interferon-β1, interleukin-6, interferon regulatory factor 5, interferon regulatory factor 8, interferon-induced guanylate-binding protein 2, tumor necrosis factor receptor superfamily member 12a, chemokine 2, chemokine CXC ligand 9, chemokine CXC motif 11, and resistin-like molecule α.

[0021] Advantages of the present invention: The interfering peptide targeting the STING protein effectively inhibits the oligomerization of the STING protein. Compared with traditional small molecule drugs, the interfering peptide of the present invention can effectively block the cross-linking of the STING protein through disulfide bonds; the interfering peptide targeting the STING protein contains a transmembrane sequence, which can directly enable the peptide segment to pass through the cell membrane and enter the cytoplasm to play a role without any carrier, avoiding the toxic and side effects caused by the carrier; D-type amino acids are degraded more slowly in animals than natural L-type amino acids. Modifying the interfering peptide into a D-type amino acid reverse (D-retroinverso, hereinafter referred to as "DRI") isomer makes the interfering peptide have good tolerance and therapeutic effect. Therefore, the DRI-modified interfering peptide targeting the STING protein has the feasibility of conducting clinical trials; at the same time, the interfering peptide of the present invention is only a 25-amino acid small peptide, which has no immunogenicity or extremely low immunogenicity and can avoid causing hypersensitivity reactions; in addition, the interfering peptide of the present invention can be directly obtained through existing mature polypeptide synthesis technologies, and has advantages such as high purity, controllable quality, and great drug development potential. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is a structural diagram of the STING protein and a schematic diagram of the target sequence of the interfering peptide, where SIP-III represents the interfering peptide, the same below, TM represents the transmembrane domain, CBD represents the cytoplasmic ligand-binding domain, and CTT represents the C-terminal tail;

[0023] Figure 2 It is a schematic diagram of detecting the molecular weight of the synthesized interfering peptide by mass spectrometry (MS);

[0024] Figure 3 It is a schematic diagram of detecting the purity of the synthesized interfering peptide by high performance liquid chromatography (HPLC);

[0025] Figure 4 It is a result diagram of detecting the dimerization of the STING protein and the transduction activation of downstream signals after treatment with the interfering peptide by Western Blot, where "+" represents the addition of the interfering peptide and "-" represents the non-addition of the interfering peptide;

[0026] Figure 5 It is a result diagram of detecting the effect of the interfering peptide treatment on the liquid-liquid phase separation ability of the STING protein by immunofluorescence;

[0027] Figure 6 It is a schematic diagram of detecting the mRNA expression of inflammatory factors in the spleen, liver, and lung tissues of ACE2 transgenic mice treated with the interfering peptide and infected with SARS-CoV-2 by qPCR experiment, where the fold change is used to represent the expression difference of the gene under different conditions;

[0028] Figure 7Schematic diagram of detecting lung inflammatory injury in ACE2 transgenic mice treated with interfering peptides and infected with SARS-CoV-2 by hematoxylin-eosin (HE) staining;

[0029] Figure 8 Schematic diagram of the body weight of ACE2 transgenic mice treated with interfering peptides and infected with SARS-CoV-2 detected by statistical experiments;

[0030] Figure 9 Schematic diagram of detecting the polymerization of STING protein in the lungs of ACE2 transgenic mice treated with interfering peptides and infected with SARS-CoV-2 by immunofluorescence experiment. Detailed implementation manners

[0031] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the exemplified embodiments are not used as a limitation to the present invention.

[0032] Embodiment 1

[0033] As Figure 1 shown, the design idea of the interfering peptide drug in this embodiment is as follows: First, design an interfering peptide segment targeting the amino acids at positions 286-298 near the disulfide bond formation site region within the STING protein molecule. The amino acid sequence of this segment is IDELTRCFLKAQE. The natural amino acids are L-type. Design D-type short peptides to specifically disrupt the interaction between STING proteins and avoid their formation of high polymers leading to excessive activation of downstream signals.

[0034] Secondly, in order to promote the absorption of the interfering peptide by cells, the interfering peptide segment is designed to be fused with a transmembrane sequence (HIV-TAT). HIV-TAT is a hydrophilic sequence with the amino acid sequence GRKKRRQRRRPP, which can enable the peptide segment to cross the cell membrane and be absorbed by cells in an energy-independent manner.

[0035] Then, DRI modification of the peptide segment can improve the stability and effectiveness of the peptide segment in cell and animal experiments. Modify the entire interfering peptide segment into an inverse isomer. Finally, the amino acid sequence of the interfering peptide is IDELTRCFLKAQEPPRRRQRRKKRG (SEQ ID NO.1). It is synthesized by GL Biochem (Shanghai) Ltd. using D-type amino acids as raw materials.

[0036] As Figure 2 shown, the synthesized interfering peptide was identified by matrix-assisted laser desorption / ionization time-of-flight mass spectrometry liquid chromatography-mass spectrometry system to have a molecular weight of 3138.64 Da.

[0037] As Figure 3As shown in the figure, high performance liquid chromatography (HPLC) used an Inertsil ODS-SP liquid chromatography column (Shimadzu, 4.6 mm × 250 mm) as the stationary phase, and gradient elution was performed using mobile phase A (100% acetonitrile, 0.1% trifluoroacetic acid) and mobile phase B (100% ultrapure water, 0.1% trifluoroacetic acid). After HPLC identification, the purity was greater than 98%.

[0038] Example 2

[0039] 1. Experimental materials

[0040] The interfering peptide prepared in Example 1, 2'3'-cyclic guanosine monophosphate (2'3'-cGAMP), fetal bovine serum, Dulbecco's Modified Eagle Medium (DMEM medium), penicillin / streptomycin solution (from Gibco), human monocytic leukemia cell line (THP-1 cell line) from ATCC, STING protein antibody, serine / threonine protein kinase antibody (TBK1 antibody), phosphorylated serine / threonine protein kinase antibody (p-TBK1 antibody), phosphorylated interferon regulatory factor 3 antibody (p-IRF3 antibody), interferon regulatory factor 3 antibody (IRF3 antibody), actin antibody (Actin antibody) and related secondary antibodies (from CST).

[0041] 2. Experimental methods

[0042] The THP-1 cell line was seeded in a 12-well plate. When the cell density reached 90%, cells in 4 wells were treated with 100 μM interfering peptide for 0, 2, 4, and 6 h respectively, and then stimulated with 2'3'-cGAMP. After 2 h, the cells were collected, and the oligomerization of STING protein and the phosphorylation of downstream key kinases TBK1 and IRF3 were detected by Western Blot.

[0043] 3. Experimental results

[0044] As Figure 4 shown, the oligomerization state of STING protein plays a core role in its activation and downstream signal transduction, and is an important link in regulating the immune response. However, the over-activation of STING protein will lead to the production of excessive cellular inflammatory factors, resulting in tissue and organ damage. In this example, after treating cells with the interfering peptide, almost no oligomerization of STING protein was observed in the non-reducing gel electrophoresis diagram, indicating that the interfering peptide can significantly inhibit the oligomerization of STING protein induced by 2'3'-cGAMP. At the same time, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, after adding the interfering peptide for 2 - 6 h, the phosphorylation levels of TBK1 and IRF3 were significantly reduced, indicating that the interfering peptide can significantly inhibit the phosphorylation of downstream key protein kinase TBK1 and transcription factor IRF3.

[0045] Example 3

[0046] 1. Experimental materials

[0047] The interfering peptide prepared in Example 1, bovine serum albumin (BSA), 2'3'-cGAMP, 4% paraformaldehyde / PBS, 0.1% polyethylene glycol octylphenyl ether (TritonX-100), fluorescein isothiocyanate-labeled rabbit anti-sheep immunoglobulin G, rhodamine-labeled sheep anti-mouse immunoglobulin G, STING protein (from CST), TBK1 antibody (from Santacruz), 4',6-diamidino-2-phenylindole (DAPI).

[0048] 2. Experimental methods

[0049] The control group was treated with 100 μM BSA (i.e., Figure 5 the BSA group), and the experimental group was treated with 100 μM interfering peptide for 2 and 6 h respectively, and the cells were stimulated with 1 μg / mL 2'3'-cGAMP. After 1 h, the cells were collected, fixed and perforated with 4% paraformaldehyde / PBS solution, then STING protein and TBK1 antibody were added and incubated overnight, and then fluorescein isothiocyanate-labeled rabbit anti-sheep immunoglobulin G and rhodamine-labeled sheep anti-mouse immunoglobulin G were added and incubated at room temperature for 1 h, and the coverslips were sealed and observed under a confocal microscope.

[0050] 3. Experimental results

[0051] As Figure 5 shown, after stimulation with 2'3'-cGAMP, strong liquid-liquid phase separation (LLPS) of STING protein occurred in the cells in the control group, forming spherical spots, and there was co-localization with the condensate of TBK1; after treatment with 100 μM interfering peptide for 2 h, the spheroid-forming ability of STING protein was weakened, and the co-localization with the condensate of TBK1 decreased. After treatment with 100 μM interfering peptide for 6 h, the liquid-liquid phase separation of STING protein was completely inhibited, and the co-localization with the condensate of TBK1 was significantly lower than that of the control group and the 2 h treatment group. The above results indicate that the interfering peptide significantly inhibits the interaction between STING protein and TBK1 kinase, providing strong support for inhibiting downstream signal transduction.

[0052] Example 4

[0053] 1. Experimental materials

[0054] ACE2 transgenic mice (transgenic mice stably expressing human angiotensin-converting enzyme 2), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the interfering peptide prepared in Example 1, guanidine isothiocyanate-phenol (Trizol, from TAKARA), qPCR kit. Table 1 shows the primers required for qPCR (the required primers were synthesized by Youkang Biotechnology Co., Ltd.). The inflammatory factors detected include interferon beta 1 (IFN-β1), interleukin-6 (IL-6), interferon regulatory factor 5 (Irf5), interferon regulatory factor 8 (Irf8), interferon-induced guanylate-binding protein 2 (Gbp2), tumor necrosis factor receptor superfamily member 12A (Tnfrsf12a), chemokine 2 (Ccl2), chemokine CXC ligand 9 (Cxcl9), chemokine CXC motif ligand 11 (Cxcl11), resistin-like molecule alpha (Retnla), coagulation factor III (F3).

[0055] Table 1 Primers required for qPCR

[0056] 2. Experimental methods

[0057] Dissolve the interfering peptide with sterile phosphate buffer (PBS) to a concentration of 1 mg / mL. The ACE2 transgenic mice were divided into 3 groups, with 6 mice in each group. The first group and the second group were respectively injected with 0.5 mL of sterile PBS as controls, and the third group was injected with 0.5 mg of the interfering peptide. One hour later, the mice in the second group and the third group were anesthetized and inoculated intranasally with SARS-CoV-2 virus, and each mouse was inoculated with approximately 1×10 5 50% tissue culture infective dose (TCID 50 50) of SARS-CoV-2 virus. Sixteen hours after virus infection, the spleen, liver, and lung tissues of the mice were taken, and total RNA was extracted using the guanidine isothiocyanate-phenol method (Trizol method). After reverse transcription, the expression of inflammatory factor mRNAs in the spleen, liver, and lung tissues was detected by qPCR. The statistical analysis of the results was expressed as "mean ± standard error of the mean" (mean ± SEM), and ANOVA was used for comparison, p <0.05 was considered a significant difference, p <0.01 was considered a highly significant difference.

[0058] 3. Experimental results

[0059] As Figure 6As shown, the content of cellular inflammatory factors in ACE2 mice in the SARS-CoV-2 + SIP-III group was significantly lower than that in ACE2 mice in the SARS-CoV-2 + PBS group, indicating that the interfering peptide could significantly reduce the transcriptional production of cellular inflammatory factor mRNA induced by SARS-CoV-2 in the tissues of ACE2 transgenic mice.

[0060] Example 5

[0061] 1. Experimental materials

[0062] ACE2 transgenic mice, SARS-CoV-2, the interfering peptide prepared in Example 1, and materials and reagents related to tissue fixation, embedding, and HE staining (provided by Shanghai Sangon Biotech Co., Ltd.).

[0063] 2. Experimental method

[0064] Dissolve the interfering peptide with sterile PBS to a concentration of 1 mg / mL. The ACE2 transgenic mice were divided into 3 groups. The first group was only injected with 0.5 mL of sterile PBS. The second group was injected with 0.5 mL of sterile PBS, and 1 hour later, intranasally inoculated with 1×10 5 TCID 50 of SARS-CoV-2. The third group was injected with 0.5 mg of the interfering peptide, and 1 hour later, intranasally inoculated with 1×10 5 TCID 50 of SARS-CoV-2. 24 hours after virus infection, the lung tissues of the mice were taken and fixed in 4% paraformaldehyde / PBS for tissue fixation, and paraffin sections of the lung tissues were made. The pathological changes in the lungs of the mice were detected by HE staining.

[0065] 3. Experimental results

[0066] As Figure 7 shown, the interfering peptide could significantly reduce the lung lesions in ACE2 transgenic mice caused by SARS-CoV-2 infection. The lung tissue morphology of the mice not infected with the virus (PBS group) was normal, the alveoli were clear, and the septa were slender. In the SARS-CoV-2 + PBS group, the alveolar septa were significantly thickened, and hemagglutination and inflammatory cell infiltration caused by virus infection were visible locally, proving that virus infection caused an obvious inflammatory response. In the SARS-CoV-2 + SIP-III group, the thickening of the alveolar septa was not obvious, and the phenomena of hemagglutination and inflammatory cell infiltration were significantly lower than those in the SARS-CoV-2 + PBS group.

[0067] Example 6

[0068] 1. Experimental materials

[0069] ACE2 transgenic mice, SARS-CoV-2, the interfering peptide prepared in Example 1, etc.

[0070] 2. Experimental methods

[0071] Dissolve the interfering peptide with sterile PBS to a concentration of 1 mg / mL. The ACE2 transgenic mice were divided into 3 groups. The first group was injected only with 0.5 mL of sterile PBS, the second group was injected with 0.5 mL of sterile PBS, and 1 hour later, they were inoculated intranasally with 1×10 5 TCID 50 of SARS-CoV-2. The third group was injected with 0.5 mg of the interfering peptide, and 1 hour later, they were inoculated intranasally with 1×10 5 TCID 50 of SARS-CoV-2. After 24 hours of SARS-CoV-2 infection, the body weight changes of the mice were observed and weighed every day. After 7 days of infection, the statistics were ended.

[0072] 3. Experimental results

[0073] As Figure 8 shown, the interfering peptide can significantly alleviate the weight loss of ACE2 transgenic mice caused by SARS-CoV-2 infection. The body weight of the mice not infected with the virus (PBS group) gradually increased within one week, while the body weight of the mice in the SARS-CoV-2 + PBS group gradually decreased. The SARS-CoV-2 + SIP-III group alleviated the weight loss of the mice to a certain extent.

[0074] Example 7

[0075] 1. Experimental materials

[0076] ACE2 transgenic mice, SARS-CoV-2, the interfering peptide prepared in Example 1, and tissue fixation and embedding related materials and reagents such as paraformaldehyde are all domestic. Rabbit anti-STING protein (from CST), DAPI, and fluorescein isothiocyanate-labeled rabbit anti-sheep immunoglobulin G.

[0077] 2. Experimental methods

[0078] Dissolve the interfering peptide with sterile PBS to a concentration of 1 mg / mL. The ACE2 transgenic mice were divided into 3 groups. The first group was only injected with 0.5 mL of sterile PBS, the second group was injected with 0.5 mL of sterile PBS, and 1 hour later, they were inoculated intranasally with 1×10 5 TCID 50 of SARS-CoV-2. The third group was injected with 0.5 mg of the interfering peptide, and 1 hour later, they were inoculated intranasally with 1×10 5 TCID 50SARS-CoV-2. Twenty-four hours after SARS-CoV-2 infection, mouse lung tissues were taken, fixed in 4% paraformaldehyde / PBS, and paraffin sections of lung tissues were made. The expression of STING protein in mouse lungs was detected by immunofluorescence.

[0079] 3. Experimental Results

[0080] As Figure 9 shown in the figure, in this example, the aggregation of STING protein was detected by a fluorescent secondary antibody conjugated with fluorescein isothiocyanate. There was almost no aggregated fluorescence signal in the lung tissues of mice not infected with the virus (PBS group), while there was a strong STING aggregated fluorescence signal in the lung tissues of mice in the SARS-CoV-2 + PBS group, and only a weak signal of STING protein aggregation could be detected in the lung tissues of mice in the SARS-CoV-2 + SIP-III group.

[0081] Obviously, the above examples are only for clear illustration and not limitations on the implementation methods. For those of ordinary skill in the art, other different forms of changes or variations can be made based on the above description. It is not necessary and impossible to enumerate all implementation methods here. And the obvious changes or variations derived therefrom are still within the protection scope of the present invention.

Claims

1. Use of an interfering peptide that inhibits the interaction of stimulator of interferon genes in the preparation of a drug for preventing or treating viral infections, characterized in that, The amino acid sequence of the interfering peptide is as shown in SEQ ID NO.

1.

2. The application according to claim 1, characterized in that, The virus includes Severe Acute Respiratory Syndrome Coronavirus 2.

3. An interfering peptide that inhibits the interaction of stimulator of interferon genes, characterized in that, The amino acid sequence of the interfering peptide is as shown in SEQ ID NO.

1.

4. The interfering peptide according to claim 3, wherein The interfering peptide is a D-amino acid reverse isomer.

5. A drug for inhibiting hemagglutination, characterized in that, The drug includes the interfering peptide described in claim 3 or 4.

6. A drug for inhibiting serine-threonine protein kinase phosphorylation, characterized in that, The drug includes the interfering peptide described in claim 3 or 4.

7. An immunosuppressive composition, characterized in that, The immunosuppressive composition includes the interfering peptide described in claim 3 or 4.

8. Use of the interfering peptide described in claim 3 or 4 in the preparation of an inhibitor of interferon gene-stimulating factor.

9. A drug for inhibiting the interaction of stimulator of interferon genes, characterized in that, The drug includes the interfering peptide described in claim 3 or 4.

10. Use of the interfering peptide according to claim 3 or 4 in the preparation of an anti-inflammatory product, characterized in that, The anti-inflammatory product inhibits the production of inflammatory factors, wherein the inflammatory factors are selected from one or more of interferon β1, interleukin-6, interferon regulatory factor 5, interferon regulatory factor 8, interferon-induced guanylate-binding protein 2, tumor necrosis factor receptor superfamily member 12a, chemokine 2, chemokine CXC ligand 9, chemokine CXC motif 11, and resistin-like molecule α.

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