A TAOK3 inhibitor and use of TAOK3 and its inhibitor in regulating the innate immune system

Abstract

The present invention relates to the technical field of immunomodulatory drugs, and specifically to a TAOK3 inhibitor and the use of TAOK3 and its inhibitors in regulating the innate immune system. The inventors have conducted in-depth research on the intracellular innate immune network mediated by mitochondria and MAVS, and discovered for the first time that TAOK3 (TAO Kinase 3) plays an important role in the above-mentioned signaling pathway, and can be used as a drug target for the production and preparation of drugs that enhance innate immunity and the screening of related drugs. In addition, the present technical solution further screened TAOK3 to obtain the TAOK3 inhibitor CP43 that can effectively activate innate immunity and has antiviral ability. The present technical solution solves the technical problem of the lack of drug targets and related drugs for activating the innate immune system in the prior art, enhances innate immunity, and improves the body's antiviral ability, and has broad application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of immunomodulatory drugs, and in particular to a TAOK3 inhibitor and applications of TAOK3 and its inhibitor in regulating the innate immune system. Background Art

[0002] The innate immune system is different from the adaptive immune system and is an immune system that can sense self and non-self. It plays a vital role in resisting microbial infection, inhibiting the occurrence of tumors and autoimmune diseases. By identifying pathogens through pattern recognition receptors, the body will activate signals to mobilize various immune cells to kill pathogens. More specifically, the innate immune system is gradually formed in the long-term evolution of organisms. It has broad specificity and is the first line of defense against foreign invasion. The innate immune system can recognize pathogen-associated pattern molecules (PAMPs) through a class of pattern recognition receptors (PRRs), thereby initiating innate immunity to achieve cell phagocytosis, the synthesis and secretion of a series of inflammatory cytokines and chemokines, upregulating the expression of co-stimulatory molecules on the surface of antigen-presenting cells, inducing T or B lymphocytes to differentiate into effector T or B cells, and ultimately strengthening acquired immunity.

[0003] Since innate immunity plays an important role in resisting foreign invasion of pathogens, the regulation of this signaling pathway is also very precise, and it will be closed by the negative feedback regulatory mechanism after the response is completed. After normal cells in the body mutate, they will also be recognized by the body's innate immune system and thus be eliminated. However, some cancer cells will enhance the negative feedback regulatory mechanism to inhibit the activity of innate immunity, thereby escaping immune surveillance. In 2005, four research groups reported that mitochondrial antiviral signaling protein (MAVS) plays a core regulatory role in innate immunity. It is located in mitochondria and serves as a platform for the aggregation of antiviral complexes to promote signal transduction. After the virus infects the host, cell pattern recognition receptors such as Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) recognize the invading pathogens and transmit signals to MAVS. After MAVS is activated, its conformation changes, and then downstream related molecules are recruited. Through cascade reactions, it finally activates related signaling pathways such as NF-κB and IRF3, inducing the expression of type I interferons (α and β) and other related factors as well as cellular innate immune responses. Therefore, the regulation of MAVS has become the main battlefield for fighting foreign substances and identifying mutated cancer cells. However, the intracellular innate immune network mediated by mitochondria and MAVS needs to be refined and improved. It is necessary to fully study the MAVS signaling pathway and further discover the regulatory factors related to it, so as to provide references for discovering new drug targets and developing new drugs to regulate innate immunity. Summary of the invention

[0004] The present invention is intended to provide the use of TAOK3 in the preparation of drugs for enhancing natural immunity, so as to solve the technical problem of the lack of drug action targets and related drugs for activating the natural immune system in the prior art.

[0005] In order to achieve the above object, the present invention adopts the following technical scheme:

[0006] Application of TAOK3 in the preparation of drugs for enhancing natural immunity.

[0007] This scheme also provides an application of TAOK3 in screening drugs that enhance natural immunity.

[0008] The principle and beneficial effects of this scheme are:

[0009] Since innate immunity plays an important role in resisting foreign invasion of pathogens, and mitochondrial antiviral signaling protein (MAVS) plays a core regulatory role in innate immunity, the inventors have conducted in-depth research on the intracellular innate immune network mediated by mitochondria and MAVS. It was discovered for the first time that TAOK3 (TAO Kinase 3) plays an important role in the above signaling pathway, and can be used as a drug target in the production and preparation of drugs that enhance innate immunity. The above drugs have the functions of inhibiting TAOK3 protein activity or reducing TAOK3 protein expression level or Taok3 gene expression level or Taok3 gene transcription level, thereby preventing MAVS degradation, enhancing MAVS-mediated intracellular innate immune response, achieving cell phagocytosis, synthesis and secretion of a series of inflammatory cytokines and chemokines, upregulating the expression of co-stimulatory molecules on the surface of antigen-presenting cells, inducing T or B lymphocytes to differentiate into effector T or B cells, and ultimately strengthening acquired immunity. In addition, by utilizing the performance of TAOK3, we can establish relevant in vitro or in vivo models to screen candidate drugs that have antiviral effects that enhance natural immunity or rely on natural immunity to obtain drugs with the best performance.

[0010] During the research, the inventors constructed cell lines with upregulated expression of TAOK3 and knockout of TAOK3, and found that the deletion of the Taok3 gene significantly increased the mRNA transcription levels of cellular antiviral-related proteins IFN-β1, RANTES and ISG15 (Example 1). - / - cells, found that relative to TAOK3 + / + Cells, TAOK3 - / - The cells have stronger antiviral ability, and the mRNA transcription levels of antiviral related proteins IFN-β1, RANTES and ISG15 increased significantly after knocking out TAOK3, indicating that TAOK3 protein or Taok3 gene is a key target for enhancing the body's antiviral ability (Examples 2 and 3). The inventors used IFN-β1 as the target of action and studied the effect of TAOK3 on the natural immune process. It was found that TAOK3 can specifically inhibit the transcriptional activation of IFN-β induced by Sendai virus, and has a significant effect on the protein level of MAVS (Examples 4 and 5).

[0011] In summary, TAOK3 can be used in the actual operation of preparing drugs that enhance natural immunity, especially for the preparation of antiviral drugs that rely on natural immunity. Moreover, TAOK3, as a newly discovered drug target, can be used for the screening of related drugs that enhance natural immunity, especially antiviral drugs that rely on natural immunity. In this technical solution, the inventors screened CP43 as a drug that enhances natural immunity and increases the body's ability to resist viral infection by using TAOK3 as a drug target.

[0012] Furthermore, the drug is used to increase the level of MAVS protein. The kinase activity of TAOK3 protein is inhibited or the expression level is reduced, which can effectively inhibit the degradation of MAVS, increase the level of MAVS protein, enhance innate immunity, and improve the body's antiviral ability. In addition, TAOK3 protein can be used as a regulatory agent for MAVS protein, and then applied to the study of the mechanism of action of MAVS protein.

[0013] Furthermore, the drug is used to increase the transcription level of antiviral related genes, including Ifn-β1 gene, Rantes gene and Isg15 gene. Experiments have shown that the kinase activity of TAOK3 protein is inhibited or the expression level is reduced, and the transcription level of antiviral related genes such as Ifn-β1 gene, Rantes gene and Isg15 gene is increased, thereby enhancing innate immunity and improving the body's antiviral ability. The means or reagents used to reduce the expression level of TAOK3 protein (such as CP43 or gene knockout means, etc.) can be used as transcription inhibitors or inhibition methods of Ifn-β1 gene, Rantes gene and Isg15 gene, and can be used in the study of the mechanism of action and signal pathways of these genes.

[0014] Furthermore, the drug is used for antiviral treatment. The kinase activity of TAOK3 protein is inhibited or the expression level is reduced, and cells can resist viral infection more effectively. In particular, by enhancing the natural immune response of cells, the antiviral effect of natural immunity is improved.

[0015] Furthermore, the drug is used to inhibit the activity of TAOK3 protein or reduce the expression level of TAOK3 protein or reduce the expression level of Taok3 gene or reduce the transcription level of Taok3 gene. By inhibiting TAOK3 at the protein level and gene level, the body's natural immunity level can be effectively improved, as well as the body's antiviral ability.

[0016] Furthermore, the drug is CP43.

[0017] The inventors found that CP43 has a relatively ideal effect of inhibiting the activity of TAOK3 protein, and can be applied to drugs that enhance natural immunity and enhance antiviral effects, thereby achieving therapeutic effects mediated by the TAOK3 drug target.

[0018] This solution also provides a TAOK3 inhibitor, which is CP43 with a chemical formula as shown in formula (1); it is used to inhibit viral infection;

[0019]

[0020] This scheme also provides an application of CP43 in the preparation of a reagent for enhancing natural immunity.

[0021] The principle and beneficial effect of this scheme are: due to the discovery of TAOK3, a drug target for enhancing natural immunity and antiviral effects, the inventors want to further find convenient and reliable substances that can be used to inhibit TAOK3 protein activity or reduce TAOK3 protein expression levels or reduce Taok3 gene expression levels or reduce Taok3 gene transcription levels. There are no reports of relevant inhibitors of TAOK3 itself. After a large number of screening studies, the inventors found that CP43 has the effect of inhibiting TAOK3 activity, and the antiviral effect can be achieved in the mouse model by the simple means of intraperitoneal + tail vein injection. Therefore, the TAOK3 inhibitor CP43 can be used in the preparation of reagents for enhancing natural immunity.

[0022] Furthermore, the drug is used for antiviral treatment or for enhancing natural immunity by increasing the level of MAVS protein.

[0023] The inventors used CP43 to treat virus-infected cells and model animals, and through plaque detection, flow cytometry detection, qPCR detection, mouse survival time analysis and other methods, they found that CP43 has an ideal antiviral effect and can be used to enhance MAVS-mediated intracellular innate immune response. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 TAOK3 of Example 1 - / - Cells and TAOK3 + / + Immunoblot images of cells.

[0025] Figure 2 TAOK3 of Example 2 - / - Cells and TAOK3 + / + Statistical graph of qRT-PCR results of antiviral-related proteins in cells.

[0026] Figure 3 TAOK3 of Example 3 - / - Cells and TAOK3+ / + The antiviral ability of cells was detected by crystal violet staining and the statistical results were obtained.

[0027] Figure 4 TAOK3 of Example 3 - / - Cells and TAOK3 + / + Microscopic and fluorescent images of cells' antiviral ability detection.

[0028] Figure 5 TAOK3 of Example 3 - / - Cells and TAOK3 + / + Flow cytometry results of antiviral ability testing of cells.

[0029] Figure 6 This is the result of studying the effect of TAOK3 on the expression of antiviral related protein IFN-β in Example 4.

[0030] Figure 7 This is the target protein screening result of TAOK3 in the natural immune pathway of Example 5.

[0031] Figure 8 The immunoprecipitation and immunoblotting analysis results of Example 6 are shown in FIG.

[0032] Fig. 9 These are cell photographs and fluorescent images of the study on the antiviral effect of CP43 in Example 7.

[0033] Fig.10 This is the flow cytometry detection result of Example 7.

[0034] Fig.11 This is the plaque analysis detection and statistical results of Example 7.

[0035] Fig.12 This is a statistical graph of the qRT-PCR results of antiviral-related proteins under the action of CP43 in Example 7.

[0036] Fig.13 This is the mouse survival curve of Example 8.

[0037] Fig.14 This is the mouse serum plaque test result of Example 8.

[0038] Fig.15 This is the statistics of serum virus copy number in Example 8. DETAILED DESCRIPTION

[0039] The present invention is further described in detail below in conjunction with the examples, but the embodiments of the present invention are not limited thereto. Unless otherwise specified, the technical means used in the following examples and experimental examples are conventional means well known to those skilled in the art, and the materials, reagents, etc. used can be obtained from commercial channels. Unless otherwise specified, the technical means used in the following examples are conventional means well known to those skilled in the art; the experimental methods used are all conventional methods.

[0040] Example 1: Construction of TAOK3 knockout and TAOK3 overexpression cell lines

[0041] The TAOK3 (NCBI Gene ID: 51347) knockout cell line in this example is realized by the conventional CRISPR / Cas9 system in the prior art, and the commercially available CRISPR / Cas9 system expression vector lenti V2 is used to construct the gene knockout expression vector. The general process of constructing the TAOK3 knockout cell line is as follows:

[0042] (1) sgRNA expression vector (gene knockout expression vector):

[0043] After annealing, sgRNA oligos (F and R) form a double-stranded structure, which is then connected and integrated with an empty vector (lenti V2) for expression by conventional means to construct an sgRNA expression vector. The cDNA sequence of sgRNA oligo is as follows:

[0044] The DNA sequences of the sgRNA oligos are:

[0045] F:5'-caccGCGATCTCCACTTCCTGAAG-3'(SEQ ID NO.1);

[0046] R: 5'-aaacCTTCAGGAAGTGGAGATCGC-3' (SEQ ID NO. 2).

[0047] (2) TAOK3 knockout cell line (TAOK3 - / - cell)

[0048] After the sgRNA expression vector was successfully constructed, conventional virus packaging was performed, and then the packaged virus was used to infect HEK293T cells to establish a TAOK3 knockout cell line (TAOK3 - / - cell).

[0049] In addition, in order to conduct subsequent TAOK3 efficacy research, this technical solution also constructed a TAOK3 expression vector. The general construction process is as follows: first, PCR amplify the TAOK3 gene; then, the basic plasmid (pCMV-3Tag-1A) and the TAOK3 gene PCR amplification fragment are double-digested, and under the action of ligase, the basic plasmid and the TAOK3 gene PCR amplification fragment are connected to obtain an expression vector with the function of expressing TAOK3 protein.

[0050] The established TAOK3 knockout cell line was subjected to semi-quantitative WB detection, and GAPDH protein was used as an internal reference. The detection results are shown in Figure 1 As shown in TAOK3 + / + In cells (wild-type cells without gene knockout), TAOK3 protein is expressed in large quantities; in TAOK3 knockout cell lines, the expression of TAOK3 protein is downregulated.

[0051] Example 2: Effect of viral infection on TAOK3 - / - Cells and TAOK3 + / + Study on the influence of antiviral related proteins on cells

[0052] Infection of TAOK3 with SeV virus - / - Cells and TAOK3 + / + Cells were used for quantitative PCR detection. The specific operation process was as follows: TAOK3 - / - Cells and TAOK3 + / + The cells were 2×10 6 The cells were inoculated in a 6-well plate at an inoculum size of 100 μg / mL. After culturing for 16 h, SeV virus (Sendai virus) was added, and then the cells were collected at the specified time points. After the cells were lysed using TRIzol (TAKARA, Otsu, Japan), total cell RNA was extracted according to conventional methods in the prior art, and reverse transcription and quantitative PCR were performed using the TAKARA kit to detect the mRNA transcription levels of antiviral related proteins IFN-β1, RANTES, and ISG15. The experimental results are shown in Figure 2 As shown in the figure, the effect of TAOK3 gene knockout on the downstream genes of the antiviral innate immune pathway was explored. The results showed that the mRNA transcription levels of antiviral related proteins IFN-β1, RANTES and ISG15 were significantly increased after TAOK3 knockout.

[0053] Example 3: TAOK3 - / - Study on the antiviral ability of cells

[0054] Referring to the method in Example 2, TAOK3 was infected with GFP-VSV virus (GFP-labeled vesicular stomatitis virus) - / - Cells and TAOK3 + / +The culture supernatant was diluted (100 times, 1000 times and 10000 times) and added to Vero cells for 1 hour. Then, the cells were covered with 1% methylcellulose and cultured for 48 hours. After fixation with 4% paraformaldehyde, the unkilled cells were stained with crystal violet to calculate the virus titer. Among them, SeV, VSV and GFP-VSV can be obtained through commercial means. In this study, these viruses were all from Su Hongbing's laboratory at Wuhan University. For crystal violet staining experimental results and statistical graphs, see Figure 3 . Figure 3 In the above figure, the dilution multiples from left to right are 100 times, 1000 times and 10000 times. Figure 3 The figure below is a statistical chart of crystal violet staining results, showing GFP-VSV infection of TAOK3 - / - Cells and TAOK3 + / + After the cells were transfected, the difference in the amount of GFP-VSV virus in the supernatant (shown as the logarithm of GFP-VSV titer), TAOK3 - / - The ability of cells to resist viral infection is stronger than TAOK3 + / + Cells. Microscopic images and fluorescence images of Vero cells after 48 hours of culture covered with methylcellulose are shown in Figure 4 ,TAOK3 + / + The cell experimental group showed stronger fluorescence, which also proved that TAOK3 + / + The cells' ability to resist viral infection is poor. It is further confirmed that TAOK3 protein is a key factor in cells' resistance to viral infection, and downregulating the expression of TAOK3 protein can enhance the cells' ability to resist viral infection.

[0055] GFP-VSV virus infection TAOK3 - / - Cells and TAOK3 + / + After 16 h, the cell samples were harvested and resuspended in 0.5 ml of PBS buffer. The samples were analyzed by flow cytometry (Beckman Coulter, Fullerton, CA, USA), and the obtained data were analyzed using FlowJo software (TreeStar, Ashland, OR, USA). The experimental results are shown in Figure 5 (The left side is TAOK3 + / + Cells, TAOK3 on the right - / - The experimental results also showed that TAOK3 - / - Cells relative to TAOK3 + / + Cells have a stronger ability to resist viral infection.

[0056] Example 4: Study on the inhibitory effect of TAOK3 on the expression of IFN-β1

[0057] The IFN-β1-luciferase reporter gene plasmid (100 ng) and the constructed kinase library expression plasmid (400 ng) (the above plasmids were from the laboratory of Su Hongbing of Wuhan University and constructed according to the standard molecular biology method in the prior art) were co-transfected into HEK293T cells seeded in 24-well plates (HEK293T cells were cultured at 2×10 6 Inoculation, DMEM medium was used for 16 h before transfection), 24 h later, Sendai virus (SeV) was added to the cells (60 μL per well of a 24-well plate), and after 12 h of incubation, the cells were lysed and the lysate was collected to detect luciferase activity and screen for kinases that affect IFN-β transcription. Figure 6 The results showed that TAOK3 could specifically inhibit Sendai virus-induced IFN-β transcriptional activation. Figure 6 Among them, Vec, TAOK3 and TAOK3 TY / AF They represent an empty vector, a plasmid containing the TAOK3 kinase gene, and a plasmid containing a TAOK3 kinase mutant gene (mutations at sites 181 and 183). Under SeV infection conditions, the amount of fluorescent protein (fluorescence intensity) produced by the luciferase reporter gene is affected by the TAOK3 kinase, indicating that the TAOK3 kinase is a kinase that affects the transcription of IFN-β1.

[0058] Example 5: Screening of target proteins of TAOK3 in the innate immune pathway

[0059] The IFN-β1 reporter gene (100 ng) and the constructed kinase library expression plasmid (400 ng) were co-transfected into HEK293T cells seeded in 24-well plates. After incubation for 36 hours, the cells were lysed and the lysate was collected to detect luciferase activity and screen for proteins that affect IFN-β transcription. The experimental results are shown in Figure 7 The experimental results show that MAVS protein is a key protein that affects IFN-β transcription through TAOK3 kinase.

[0060] Example 6: Study on the interaction between TAOK3 and MAVS

[0061] HEK293T cells were co-transfected with MAVS expression plasmid, TAOK3 expression plasmid and TAOK3 mutant expression plasmid (two sites 181 and 183). MAVS protein was tagged with HA, and TAOK3 and its mutant protein were tagged with Flag. Immunoprecipitation and immunoblotting analysis were performed according to routine procedures to explore the interaction between TAOK3 and MAVS. The experimental results can be found in Figure 8 The experimental results show that there is an interaction between TAOK3 and MAVS proteins.

[0062] Example 7: Study on the antiviral effect of CP43

[0063] HEK293T cells were cultured at 2×10 6 The inoculation amount was inoculated into two 6-well cell culture plates. After culturing for 16 hours, TAOK3 inhibitor CP43 was added to one plate, and DMSO was added to the other control group. The structural formula of CP43 is shown in formula (1), and the CAS No. is 850467-66-2. It has been reported in the literature that when CP43 is used in combination with paclitaxel, CP43 reduces the drug resistance of TAOK3 overexpressing cells to paclitaxel, and CP43 can be used as a TAOK3 inhibitor (Tsung-Ching Lai, Kinase shRNA screening reveals that TAOK3 enhances microtubule-targeted drug resistance of breast cancer cells via the NF-κB signaling pathway, Cell Commun Signal. 2020 Oct 21; 18(1): 164. doi: 10.1186 / s12964-020-00600-2.). The inventors further conducted subsequent in vitro and in vivo experiments to verify that CP4 not only has the activity of inhibiting TAOK3, but can also enhance the antiviral ability of cells / organisms by inhibiting TAOK3 and enhancing natural immunity.

[0064]

[0065] 24 hours later, GFP-VSV was diluted to MOI of 0.1, 0.01, and 0.001, and added to 6-well plates to infect cells. At the same time, 1 μL of CP43 and DMSO were added to the experimental group and the control group, respectively. After 1 hour, the culture medium was discarded and replaced with fresh culture medium. 2 μL of CP43 and DMSO were added to the experimental group and the control group, respectively. After 14 hours, photos were taken to observe fluorescence, supernatants were collected, plaque detection was performed, and cells were collected for flow cytometry detection. For cell microscopic images and fluorescence images, see Fig. 9 , flow cytometry images see Fig.10 (The left is the DMSO group, the right is the CP43 group). For the results of the plaque assay, see Fig.11 ; Fig.11 The above figure is a plaque detection image. Fig.11The figure below is a statistical graph of the plaque detection results. The above plaque detection results show that the use of CP43 can inhibit the infection of the virus to the cells (shown as the logarithmic value of the GFP-VSV titer). HEK293T strain cells were infected with SeV virus, and the cells were treated with CP43 and DMSO as described above, and then the transcription levels of Infβ1 gene and Rantes gene were detected by qRT-PCR. The experimental results can be found in Fig.12 shown.

[0066] The above experimental results indicate that treating cells with CP43 can increase the resistance of cells to viral infection. Fig.12 The results of the qPCR detection experiment showed that the transcription levels of Infβ1 gene and Rantes gene increased after the use of CP43, indicating that the cells' resistance to viral infection was enhanced.

[0067] Example 8: In vivo experimental study

[0068] A total of 18 wild-type mice were divided into three groups (DMSO group, CP43 2mg / kg, CP43 4mg / kg) with 6 mice in each group. Different doses of inhibitors and DMSO were intraperitoneally injected according to different groups. After 24 hours, the same doses of inhibitors CP43 and DMSO were injected again. Then, 300μL and 400μL VSV virus were injected through the tail vein and peritoneal cavity, respectively. After 24 hours, the mouse blood samples were collected and the same doses of inhibitors CP43 and DMSO were injected again. The serum was separated and the plaque analysis was performed, and the survival time of the mice was observed. The results are shown in Fig.13 , Fig.14 (Left dilution 1x, right dilution 10x) and Fig.15 As shown, mice injected with the inhibitor CP43 survived significantly longer under viral infection than wild-type mice that were not injected with CP43; after injection of CP43, the number of viral copies in the mouse serum decreased significantly.

[0069] The above is only an embodiment of the present invention, and the common knowledge such as the known specific technical solutions and / or characteristics in the solution is not described in detail here. It should be pointed out that for those skilled in the art, without departing from the technical solution of the present invention, several modifications and improvements can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. Application of TAOK3 in the preparation of a drug for enhancing natural immunity, characterized in that: The drug is used to increase the level of MAVS protein.

2. The use of TAOK3 according to claim 1 in the preparation of a drug for enhancing natural immunity, characterized in that: The drug is used to enhance the transcription level of anti-virus related genes, and the anti-virus related genes include Ifn-β1 gene, Rantes gene and Isg15 gene.

3. The use of TAOK3 according to claim 2 in the preparation of a drug for enhancing natural immunity, characterized in that: The medicine is used for antiviral treatment.

4. The use of TAOK3 according to claim 3 in the preparation of a drug for enhancing natural immunity, characterized in that: The drug is used to inhibit the activity of TAOK3 protein or reduce the expression level of TAOK3 protein or reduce the expression level of Taok3 gene or reduce the transcription level of Taok3 gene.

5. The use of TAOK3 according to claim 4 in the preparation of a drug for enhancing natural immunity, characterized in that: The drug is CP43.

6. Application of TAOK3 in screening drugs for enhancing natural immunity, characterized in that: The drug is used to increase the level of MAVS protein.

7. Use of a TAOK3 inhibitor in the preparation of a reagent for enhancing innate immunity, characterized in that: The TAOK3 inhibitor is CP43 having a chemical formula as shown in formula (1); it is used to inhibit viral infection; TAOK3 inhibitors are used to enhance innate immunity by increasing MAVS protein levels.

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