Application of RBM25 and its related substances in antiviral infection

Abstract

The present invention relates to the field of biomedicine, and provides the antiviral infection effect of RNA binding protein RBM25 and its application. Specifically, it relates to the use of RBM25 protein, nucleic acid molecules encoding the protein, its promoter or recombinant expression vector in the preparation of products for treating viral infectious diseases and / or diseases and / or symptoms related to viral infection, and its corresponding medicine or pharmaceutical composition. RBM25 can inhibit viral invasion and infection, reduce inflammation and damage of tissues, provide a new target for the treatment of antiviral infection, and has broad application prospects.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine, and in particular to the effects, mechanisms of action, implementation methods and uses of RNA binding protein 25 (RBM25) in treating viral infectious diseases and / or diseases and / or symptoms associated with viral infections. Background Art

[0002] Viruses are highly infectious and contagious pathogenic microorganisms, and viral infections can pose a serious threat to human health. In recent years, new or re-emerging viruses such as highly pathogenic avian influenza virus, SARS-CoV-2, Ebola virus, Zika virus, and monkeypox virus have emerged, causing serious harm to public health and people's lives and health. After invading the body, viral infection affects cell physiological processes in a variety of ways, evading the host's defense mechanism, allowing it to survive, replicate, and infect more cells in the cell. The body will also activate a variety of defense mechanisms and immune responses to eliminate or control viral infections. A deeper understanding of the body's mechanisms for resisting viral infections will help prevent and treat viral infectious diseases.

[0003] Since the virus attaches to the cell, the body has stimulated different endogenous antiviral mechanisms. Except for a few viruses that can directly fuse with the cell membrane to enter the cell, most viruses promote viral internalization through the interaction between viral adsorption proteins and receptors, enter the cell through the endocytosis pathway, and initiate the intracellular replication process. In order to block viral replication, transmission or persistent infection, host-encoded proteins can act on different stages of the viral replication cycle to limit viral entry into cells, replication, assembly or release. All viruses must enter cells to initiate their replication cycle and establish infection. Most viruses enter through the endosomal pathway of the cell through receptor-mediated endocytosis. Entering the cell is the first step in the viral infection cycle. Therefore, it is possible to develop drugs and treatments with broad-spectrum antiviral properties by targeting the pathways and processes of viral entry into cells. However, whether the body has key molecules that affect these antiviral mechanisms of viral invasion so that the host can exert a strong antiviral effect during viral infection is still rarely reported.

[0004] RNA-binding proteins (RBPs) are a class of proteins that can bind to specific RNA molecules. More than 2,300 different RBPs have been discovered so far. They interact with their target RNAs and form ribonucleoprotein complexes to regulate RNA metabolism and stability, including pre-mRNA splicing, cleavage and polyadenylation, RNA modification and editing, packaging and transport, localization, translation and degradation, and participate in a variety of physiological and pathological processes. Hundreds of host proteins associated with viral infection have been identified, about one-fifth of which are RNA-binding proteins. RNA-binding proteins are at the center of host-virus interactions, but so far only a few RBPs have been described in relation to viruses, and whether most family members are involved in regulating viral infection has not yet been reported.

[0005] RBM25 (RNA-binding motif protein 25), also known as S164, NET52 or RED120, has a highly conserved RNA-recognition motif (RRM) sequence in its protein sequence, with a total length of 843 amino acids, which is highly conserved in eukaryotes, suggesting that this protein has extremely important biological functions. The RRM domain can interact with a variety of protein structures to regulate the affinity and specificity of RNA binding in variable splicing. Recent studies have found that RBM25 can independently perform the pre-mRNA splicing function. In addition, RBM25 can also assemble into a splicing complex with multiple splicing cofactors SRm160 / 300 to regulate the variable splicing process of the splicing complex. At present, there are few studies on the function of RBM25 in the occurrence of diseases. Through RO-seq and RNA-Seq, it was found that knocking out RBM25 can affect the transcription levels of more than 500 genes. RBM25 is widely expressed in various tissues of mice and is highly expressed in mononuclear macrophages. Although the function of RBM25 in viral infectious diseases has not been reported, we reasonably speculate that RBM25 may play an important regulatory role in the process of viral infection in the body.

[0006] In summary, there is an urgent need in the art to develop an active substance that can effectively block viral invasion, effectively resist viral infection and control tissue inflammatory damage caused by viral infection, so as to control viral infectious diseases and their related symptoms and / or other complications. Summary of the invention

[0007] The present invention is aimed at the above problems and observes the effects of RBM25 on the invasion, replication and infection of multiple viruses in macrophages, and also observes the effects of RBM25 on the viral replication levels and tissue inflammatory damage in organs after multiple viral infections in mice, thereby determining the role of RBM25 in resisting viral invasion and infection.

[0008] The research process of the present invention is as follows:

[0009] We constructed a conditional knockout of RBM25 in myeloid cells (RBM25 fl / fl Lyz2-Cre + / - mice, referred to as cKO mice) and control mice (RBM25 fl / fl Lyz2-Cre - / - , referred to as WT mice). Peritoneal macrophages of RBM25 WT and cKO mice were obtained, and the above macrophages were infected with vesicular stomatitis virus (VSV), herpes simplex virus (HSV-1), and influenza A virus PR8 (IAV). The replication levels of VSV, HSV-1, and IAV were detected, and it was found that the replication levels of the above three viruses in the peritoneal macrophages of RBM25 cKO mice were significantly increased. VSV was given to RBM25 cKO and WT mice, and the viral replication and inflammatory damage in the liver and lung tissues were detected. It was found that the VSV viral replication level in the liver and lung tissues of RBM25 cKO mice was significantly higher than that of WT mice. Pathological staining showed that the hemorrhage, inflammatory cell infiltration, and cell necrosis in the liver and lung tissues of RBM25 cKO mice were more severe.

[0010] After using siRNA targeting RBM25 to interfere with the expression of RBM25 in macrophages, it was found that interfering with RBM25 did not affect the adsorption of multiple viruses on the cell surface, but promoted the invasion of different viruses into macrophages. We further constructed RBM25 overexpression lentivirus and control virus, transfected macrophages to overexpress RBM25, and found that the replication levels of VSV, HSV-1 and IAV viruses in macrophages overexpressing RBM25 were significantly lower than those in the control group. These results indicate that RBM25 inhibits the invasion and infection of multiple viruses into macrophages, thereby reducing the level of viral replication in cells and tissues and virus-mediated tissue inflammatory damage, revealing that RBM25 plays an important role in resisting viral infection.

[0011] One of the main purposes of the present invention is to provide the use of RBM25, nucleic acid molecules encoding the protein, promoters thereof or recombinant expression vectors thereof in antiviral infection, and further provide their use in treating viral infectious diseases and related diseases or symptoms. The drugs or pharmaceutical compositions disclosed herein can be used to effectively resist viral infection and control the occurrence of infectious diseases.

[0012] In some aspects disclosed in the present invention, provided are uses of RBM25, nucleic acid molecules encoding the protein, and promoters thereof in the preparation of products for treating viral infectious diseases and / or diseases and / or symptoms associated with infection.

[0013] In other aspects of the present invention, products are provided that contain RBM25, nucleic acid molecules encoding the protein, and promoters thereof as active ingredients.

[0014] In other aspects of the present invention, a method for treating infectious diseases and / or infection-related diseases and / or symptoms is also provided, the method comprising administering to a subject in need thereof a therapeutically effective amount of RBM25, a nucleic acid molecule encoding the protein, a promoter thereof, or a recombinant expression vector thereof.

[0015] In some embodiments, the RBM25 is selected from:

[0016] (a), a polypeptide having an amino acid sequence as shown in SEQ ID NO.2;

[0017] (b) a protein or polypeptide having homology or sequence identity with the amino acid sequence shown in SEQ ID NO.2 and having the ability to inhibit viral infectious diseases and / or diseases and / or symptoms associated with viral infection;

[0018] (c), a protein or polypeptide in which one or more amino acids are substituted, deleted or added in the amino acid sequence of (a) or (b) and which has the effect of inhibiting viral infectious diseases and / or diseases and / or symptoms associated with viral infection, or a protein or polypeptide derived from (a) or (b).

[0019] In some embodiments, RBM25 is: a naturally purified protein, a chemically synthesized product, or produced using recombinant technology from a prokaryotic or eukaryotic host. The host is selected from: bacteria, yeast, higher animals and mammalian cells. Preferably, it is human RBM25.

[0020] In some embodiments, the nucleic acid molecule encoding RBM25 is selected from:

[0021] (i) a nucleic acid molecule having the nucleotide sequence shown in SEQ ID NO.1;

[0022] (ii) a molecule that hybridizes to the nucleotide sequence defined in (i) under stringent conditions;

[0023] (iii) a nucleic acid molecule that is homologous to or has sequence identity with the nucleotide sequence shown in SEQ ID NO.1 and encodes a nucleic acid molecule that has the ability to inhibit viral infectious diseases and / or diseases and / or symptoms associated with viral infection;

[0024] (iv) A nucleic acid molecule encoding a nucleic acid that has the ability to inhibit viral infectious diseases and / or diseases and / or symptoms associated with viral infection, wherein one or more nucleotides are substituted, deleted or added to the nucleotide sequence in (i), (ii) or (iii).

[0025] In some embodiments, the promoter is selected from: substances that increase the level of RBM25 protein or promote the function of RBM25, such as overexpression vectors of RBM25 or RBM25 coding sequences; exogenous RBM25; naked DNA of RBM25 coding sequences; liposome-encapsulated DNA of RBM25 coding sequences; RBM25 precursor proteins or conjugates or complexes that can be converted into RBM25 in vivo.

[0026] In some embodiments, the infection is a DNA or RNA viral infection, such as an infection caused by one or more viruses selected from the group consisting of influenza virus, parainfluenza virus, respiratory syncytial virus, vesicular stomatitis virus, herpes simplex virus, varicella-zoster virus, coronavirus (such as SARS-CoV-2), enterovirus, hepatitis B virus, adenovirus, and poxvirus.

[0027] In some embodiments, the infection-related diseases and / or symptoms are one or more selected from the following groups: tissue pathological damage caused by viral infection; insufficient or excessive production of cytokines (such as interferon) after infection; endotoxic shock or death; inflammatory damage to organs; multiple organ failure, for example, the organs are selected from: lungs, liver, heart, kidneys, brain, spleen, stomach and intestines.

[0028] In some embodiments, the product is a pharmaceutical composition or a kit, for example, a pharmaceutical composition or a kit in a form suitable for administration by a method selected from the group consisting of oral administration, injection (e.g., direct naked DNA or protein injection, liposome-encapsulated DNA or protein injection), gold-coated gene gun bombardment, reproduction-defective bacteria carrying plasmid DNA, replication-defective adeno-associated virus carrying target DNA or target gene-encoded protein, electroporation, nasal administration, pulmonary administration, oral administration, and transdermal administration.

[0029] Preferably, the pharmaceutical composition or kit of the present invention comprises:

[0030] (A) a therapeutically or preventively effective amount of RBM25, a nucleic acid molecule encoding the protein, a promoter thereof and / or an inhibitor thereof;

[0031] (B) a pharmaceutically or immunologically acceptable carrier or excipient;

[0032] (C) optionally, one or more other active substances for preventing or treating viral infectious diseases and their related disorders and / or symptoms.

[0033] In some embodiments, the RBM25 vector includes a viral vector and a non-viral vector.

[0034] The "viral vector" includes adeno-associated virus and lentivirus. Suitable viral vectors are well known to those of ordinary skill in the art.

[0035] The "non-viral vector" includes liposomes or lipid complexes, cationic polymers, chitosan polymers and nanoparticle vectors, etc. Suitable non-viral vectors are well known to those skilled in the art.

[0036] Those skilled in the art may arbitrarily combine the above technical solutions and technical features without departing from the inventive concept and protection scope of the present disclosure. Other aspects of the present disclosure are obvious to those skilled in the art due to the disclosure of this article.

[0037] Beneficial protection and effects of the present invention:

[0038] The present invention provides the use of RBM25 promoters in products for treating viral infectious diseases and / or diseases and / or symptoms related to viral infection. Experiments have confirmed that RBM25 knockout promotes viral invasion and infection of cells, aggravates inflammatory cell infiltration and damage in mouse liver and lung tissues, indicating that RBM25 is a protective factor for viral infection and has the effect of inhibiting viral invasion and infection. RBM25 overexpression can inhibit viral infection, which is manifested as inhibiting viral invasion, thereby achieving the treatment of viral infectious diseases. Therefore, the present invention provides a new target for the treatment of viral infectious diseases for overexpression or functional promotion of RBM25, and has broad clinical application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The present disclosure will be further described below in conjunction with the accompanying drawings, wherein these drawings are only for illustrating the embodiments of the present disclosure rather than for limiting the scope of the present disclosure.

[0040] Figure 1 The primary peritoneal macrophages of RBM25 myeloid knockout (RBM25 cKO) and control (RBM25 WT) mice were infected with VSV, HSV-1 and IAV. The replication levels of the three viruses in RBM25 cKO cells were significantly increased. Figure A shows the mRNA expression levels of VSV, HSV-1 and IAV detected by fluorescence quantitative PCR (**, P<0.01), and Figure B shows the results of fluorescence microscopy observation of mouse peritoneal macrophages after VSV-GFP infection.

[0041] Figure 2The results showed that knocking out RBM25 promoted the replication of VSV virus in mice and aggravated the inflammatory damage of liver and lung tissues; Figure A showed the expression of VSV virus mRNA in the liver and lungs of RBM25 myeloid knockout (RBM25 cKO) and control group (RBM25 WT) mice. RBM25 knockout increased the level of VSV virus replication in the liver and lung tissues of mice (**, P<0.01); Figure B showed that eosin & hematoxylin staining showed that the inflammatory cell infiltration and cell necrosis in the liver and lung tissues of RBM25-deficient mice were more severe.

[0042] Figure 3 It shows that using siRNA interference to reduce the expression of RBM25 does not affect the adsorption of viruses to cells, but can promote virus invasion. Figure A shows that in mouse macrophages with RBM25 interference, there is no difference in the levels of VSV, HSV-1 and IAV viruses adsorbed on the cell surface; Figure B shows that after interfering with RBM25, the levels of VSV, HSV-1 and IAV viruses that invaded into cells increased (**, P<0.01).

[0043] Figure 4 It shows that overexpression of RBM25 can inhibit the level of viral replication in macrophages. The figure shows the expression levels of VSV (VSV-G), HSV (HSV TK) and IAV (IAV HA) viral mRNA in macrophages transfected with lentivirus-RBM25 and control virus by fluorescence quantitative PCR (***, P<0.001; **, P<0.01). UI: uninfected, uninfected virus group. DETAILED DESCRIPTION

[0044] The following examples and experimental examples further illustrate the present invention and should not be construed as limiting the present invention. The examples do not include a detailed description of conventional methods, such as PCR methods, methods for constructing vectors and plasmids, methods for inserting protein-encoding genes into vectors and plasmids, or methods for introducing plasmids into host cells. Such methods are well known to those skilled in the art and are described in many publications, including Sambrook, J., Fritsch, E. F. and Maniais, T. (1989) Molecular Cloning: A Laboratory Manual, 2 nd edition, Cold spring Harbor Laboratory Press.

[0045] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention, and the preferred implementation methods and materials described in the specific implementation methods are for demonstration purposes only.

[0046] Example 1: RBM25 knockout promotes cell infection with multiple viruses in vitro

[0047] Construction of RBM25 myeloid cell conditional knockout mice. fl / fl The mouse was constructed by Saiye (Suzhou) Biotechnology Co., Ltd. and then hybridized with Lyz2-Cre tool mice to obtain RBM25 fl / fl Lyz2-Cre + / - The RBM25 gene was specifically knocked out in myeloid cells, especially macrophages, and the control mice RBM25 were also obtained. fl / fl Lyz2-Cre - / - (referred to as WT mice). These mice were maintained in a special pathogen-free (SPF) environment.

[0048] Peritoneal macrophages of RBM25 WT and cKO mice were obtained, and vesicular stomatitis virus (VSV, ATCC VR-1238, MOI=1), herpes simplex virus (HSV-1, F-strain, ATCC VR-260, MOI=5), and influenza A virus PR8 (influenza A virus PR8 strain, IAV / PR8, VR-95, MOI=5) were added to the cell culture medium to infect the above macrophages. The total RNA of the macrophages was collected and the viral replication levels of VSV, HSV-1 and IAV were detected by reverse transcription-PCR and real-time quantitative fluorescence PCR.

[0049] In addition, GFP-tagged VSV virus (VSV-GFP) was used to infect peritoneal macrophages of RBM25 WT and cKO mice in vitro (MOI=1), and the viral replication in peritoneal macrophages of RBM25 WT and cKO mice was observed under a fluorescence microscope.

[0050] The results showed that compared with the control group WT mice, the replication levels of the three viruses in the peritoneal macrophages of RBM25 cKO mice were significantly increased after infection with VSV, HSV-1 and IAV viruses ( Figure 1 A), and the viral replication level of peritoneal macrophages in RBM25 cKO mice was significantly higher than that in WT group at 8h and 24h after VSV-GFP infection ( Figure 1 B).

[0051] The results showed that RBM25 knockout promoted the in vitro infection of multiple viruses (VSV, HSV-1 and IAV), suggesting that RBM25 is an endogenous protective factor for viral infection.

[0052] Example 2: RBM25 knockout promotes viral replication in mouse liver and lung tissues and aggravates tissue inflammatory damage

[0053] Construction of RBM25 myeloid cell conditional knockout mice (same as in Example 1). Control wild-type mice and myeloid cell-specific RBM25 gene knockout (RBM25 cKO) mice were intraperitoneally infected with 7×10 8 Plaque-forming units (PFU) of VSV were detected in the mice. The mice were killed 18 hours later, and the liver and lung tissues of the mice were taken to extract the total RNA of the tissues. After reverse transcription PCR, fluorescence real-time quantitative PCR was used to detect the expression of VSV virus mRNA in the liver and lungs of the mice. In addition, the liver and lung tissues were fixed with paraformaldehyde and stained with eosin and hematoxylin to observe the pathological level of the liver and lung tissues of the mice.

[0054] The results of VSV virus mRNA level detection and HE staining in mouse liver and lung tissues are shown in Figure 2 shown.

[0055] The results showed that the VSV virus mRNA levels in the liver and lung tissues of RBM25 knockout mice were significantly higher than those in wild-type mice ( Figure 2 A), Eosin & hematoxylin staining showed that the hemorrhage, inflammatory cell infiltration and cell necrosis in the liver and lung tissues of RBM25 knockout mice were more severe ( Figure 2 B).

[0056] The results showed that RBM25 knockout promoted the replication of VSV virus in vivo and aggravated inflammatory damage in liver and lung tissues, suggesting that RBM25 can play an important protective role in anti-viral infection.

[0057] Example 3: Interference in the expression of RBM25 promotes viral invasion in mouse macrophages

[0058] Primary peritoneal macrophages of wild mice were obtained and transfected with siRNA sequences targeting mouse RBM25 (sequences are shown in SEQ ID NO.3-6, synthesized by Dharmacon) and control sequences (both purchased from Dharmacon). 72 hours after the peritoneal macrophages were transfected with the above siRNA, they were pretreated at 4°C for 2 hours, VSV (MOI=5), HSV-1 (MOI=5) and IAV (MOI=5) viruses were added, and after incubation at 4°C for 1 hour, the cells were washed three times with ice-cold PBS, and the total RNA of the macrophages was collected, and the levels of VSV, HSV-1 and IAV virus adsorption were detected by reverse transcription PCR and real-time fluorescence quantitative PCR.

[0059] Similarly, primary peritoneal macrophages from wild mice were obtained and transfected with siRNA sequences targeting mouse RBM25 and control sequences for 72 hours. After pretreatment at 4°C for 2 hours, VSV (MOI=5), HSV-1 (MOI=5) and IAV (MOI=5) viruses were added. After incubation at 4°C for 1 hour, the cells were washed three times with ice-cold PBS, and preheated culture medium was added to continue culture at 37°C for 1 hour. After washing the cells three times with ice-cold PBS, the total RNA of the macrophages was collected, and the virus invasion level was detected by reverse transcription-PCR and real-time fluorescence quantitative PCR.

[0060] siRNAD-055902-01: GCGCAGGCAACCUCAAAUA (SEQ ID NO. 3);

[0061] siRNAD-055902-02:GAACGAAGAAUCCGGCCAU (SEQ ID NO.4);

[0062] siRNAD-055902-03: GCGCAACACAUUAAGAGU (SEQ ID NO. 5);

[0063] siRNAD-055902-04: GCGCAACACAUUAAGAGU (SEQ ID NO. 6).

[0064] The results showed that in mouse macrophages in which siRNA was used to interfere with RBM25, there was no difference in the levels of VSV, HSV-1, and IAV viruses adsorbed on the cell surface ( Figure 3 A), while the levels of VSV, HSV-1, and IAV that invaded macrophages increased significantly ( Figure 3 B).

[0065] The results show that using siRNA interference to reduce the expression of RBM25 does not affect the adsorption of the virus on the cell surface, but can promote the invasion of the virus, which is manifested by an increase in the number of viruses entering the cells and an enhancement of the level of viral infection.

[0066] Example 4: Overexpression of RBM25 can inhibit viral replication levels in macrophages.

[0067] Shanghai Jikai Gene Co., Ltd. was commissioned to clone and amplify the DNA fragment of the RBM25 gene and insert it into a lentivirus vector named GV643. The lentivirus overexpressing RBM25 was successfully constructed and named lentivirus-RBM25. HEK293T cells were infected with lentivirus-RBM25 and the control empty virus lentivirus-control, respectively. The infection efficiency of the lentivirus was detected by immunoblotting and immunofluorescence to confirm its overexpression effect. Then, the above lentivirus was infected in mouse peritoneal macrophages, and vesicular stomatitis virus (VSV, MOI = 1), herpes simplex virus (HSV-1, MOI = 5), and influenza A virus PR8 (IAV / PR8, MOI = 5) were added to the cell culture medium to infect the above macrophages for 8 hours. The total RNA of the macrophages was collected, and the viral replication levels of VSV, HSV-1 and IAV were detected by fluorescence real-time quantitative PCR after reverse transcription PCR.

[0068] The results showed that the replication levels of VSV, HSV-1 and IAV viruses in mouse peritoneal macrophages transfected with lentivirus-RBM25 were significantly lower than those in mouse peritoneal macrophages transfected with lentivirus-control ( Figure 4 ).

[0069] The results showed that overexpression of RBM25 can inhibit the invasion and replication of VSV, HSV-1 and IAV viruses in macrophages, suggesting that RBM25 can play an important role in resisting viral infection.

[0070] The nucleotide sequence encoding the RBM25 protein in the present invention is shown in SEQ ID NO.1:

[0071]

[0072] The amino acid sequence of the RBM25 protein in the present invention is shown in SEQ ID NO.2:

[0073] MSFPPHLNRPPMGIPALPPGIPPPQFPGFPPPVPPGTPMIPVPMSIMAPAPTVLVPTVSMVGKHLGARKDHPGLKAKENDENCGPTTTVFVGNISEKASDMLIRQLLAKCGLVLSWKRVQGASGKLQAFGFCEYKEPESTLRALRLLHDLQIGEKKLLVKVDAKTKAQLDEWKAKKKASNGNARPETVTNDDEEALDEETKRRDQMIKGAIEVLIREYSSELNAPSQESDSHPRKKKKEKKEDIFRRFPVAPLIPYPLITKEDINAIEMEEDKRDLISREISKFRDTHKKLEEEKGKKEKERQEIEKERRERERERERERERREREREREREREREKEKERERERERDRDRDRTKERDRDRDRERDRDRDRERSSDRNKDRSRSREKSRDREREREREREREREREREREREREREREREREREREKDKKRDREEDEEDAYERRKLERKLREKEAAYQERLKNWEIRERKKTREYEKEAEREEERRREMAKEAKRLKEFLEDYDDDRDDPKYYRGSALQKRLRDREKEMEADERDRKREKEELEEIRQRLLAEGHPDPDAELQRMEQEAERRRQPQIKQEPESEEEEEEKQEKEEKREEPMEEEEEPEQKPCLKPTLRPISSAPSVSSASGNATPNTPGDESPCGIIIPHENSPDQQQPEEHRPKIGLSLKLGASNSPGQPNSVKRKKLPVDSVFNKFEDEDSDDVPRKRKLVPLDYGEDDKNATKGTVNTEEKRKHIKSLIEKIPTAKPELFAYPLDWSIVDSILMERRIRPWINKKIIEYIGEEEATLVDFVCSKVMAHSSPQSILDDVAMVLDEEAEVFIVKMWRLLIYETEAKKIGLVK

[0074] The preferred embodiments of the present invention have been specifically described above, but the present invention is not limited to the embodiments. Those skilled in the art may make various equivalent modifications or substitutions without violating the spirit of the present invention. These equivalent modifications or substitutions are all included in the scope defined by the claims of this application.

Claims

1. Use of RNA binding protein RBM25 or its related substances in the preparation of drugs for treating viral infectious diseases, characterized in that: The viral infection is selected from vesicular stomatitis virus, herpes simplex virus or influenza A virus infection, The RBM25-related substance is selected from any one or more of the following: a nucleic acid encoding an exogenous RBM25 protein, a liposome or a nanomaterial encapsulating a nucleic acid encoding an RBM25 protein.

2. The use according to claim 1, characterized in that: in, The RBM25 protein is a polypeptide having an amino acid sequence as shown in SEQ ID NO.2, The nucleic acid encoding the RBM25 protein is a nucleic acid molecule having a nucleotide sequence shown in SEQ ID NO.

1.

3. Use of the RBM25 recombinant vector in the preparation of a drug for treating viral infectious diseases, characterized in that: The recombinant vector comprises an expression vector and a nucleic acid molecule encoding the RBM25 protein inserted into the expression vector, wherein the nucleic acid molecule encoding the RBM25 protein has a nucleotide sequence as shown in SEQ ID NO.

1. The viral infectious disease is selected from the group consisting of vesicular stomatitis virus, herpes simplex virus or influenza A virus infectious diseases.

4. The use according to claim 3, characterized in that The expression vector is a plasmid vector, a phage vector or a viral vector, and the viral vector is selected from adeno-associated virus or lentivirus.

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