CN-121971476-A - Application of mRNA uncapped complex subunit protein DCP1b in preparation of medicines for preventing or treating Ebola virus infection

Abstract

The present invention discloses the application of mRNA decapitated complex subunit protein DCP1b in the preparation of drugs for the prevention or treatment of Ebola virus infection. The present invention uses substances that can inhibit or reduce the expression of DCP1b to prepare products for the treatment/prevention of Ebola virus infection/proliferation or Ebola virus disease. The present invention has been experimentally proven to significantly reduce the replication of Ebola virus in cells after treatment with mRNA decapitated complex subunit protein DCP1b siRNA (DCP1b siRNA is siRNA DCP1b 245, siRNA DCP1b 901 or siRNA DCP1b 1833), proving that DCP1b siRNA can effectively inhibit the proliferation of Ebola virus. The present invention further screened for siRNA with significant knockdown effect of DCP1b, namely siRNA DCP1b 245, which has better inhibitory effect on the proliferation of Ebola virus. The present invention provides a new treatment strategy for the prevention and treatment of acute infectious diseases caused by Ebola virus infection.

Inventors

• ZHANG MENGHE
• XIE LIU
• Xu changzhi
• ZHANG BUCHANG

Assignees

• 安徽大学

Dates

Publication Date

20260505

Application Date

20260109

Claims (6)

1. 1. The application of mRNA uncapped complex subunit protein DCP1b in preparing medicines for preventing or treating Ebola virus infection is characterized in that substances capable of inhibiting or reducing expression of DCP1b are adopted to prepare products for preventing or treating Ebola virus infection/proliferation or Ebola virus diseases.
2. 2. The use according to claim 1, wherein the agent capable of inhibiting or reducing expression of DCP1b comprises, but is not limited to, a DCP1b inhibitor, a DCP1b siRNA or a gene editing tool that knocks out expression of DCP1 b.
3. 3. The use according to claim 1, wherein the DCP1b siRNA is any one of siRNA-DCP1b-245, siRNA-DCP1b-901, siRNA-DCP1 b-1833; The siRNA-DCP1b-245 is an siRNA formed by annealing two single strands shown in SEQ ID NO.1 and SEQ ID NO.2, the siRNA-DCP1b-901 is an siRNA formed by annealing two single strands shown in SEQ ID NO.3 and SEQ ID NO.4, and the siRNA-DCP1b-1833 is an siRNA formed by annealing two single strands shown in SEQ ID NO.5 and SEQ ID NO. 6; SEQ ID NO.1:5’-GGAAGGAACCUUAUUUGUUTT-3’; SEQ ID NO.2:5’-AACAAAUAAGGUUCCUUCCTT-3’; SEQ ID NO.3:5’-CAGCCAUUCAGAAACUCAUTT-3’; SEQ ID NO.4:5’-AUGAGUUUCUGAAUGGCUGTT-3’; SEQ ID NO.5:5’-GCCUAUCUCUUCAGCAUGATT-3’; SEQ ID NO.6:5’-UCAUGCUGAAGAGAUAGGCTT-3’。
4. 4. the use according to claim 1, wherein said DCP1b siRNA is siRNA-DCP1b-245 formed by annealing two single strands shown in SEQ ID No.1 and SEQ ID No. 2.
5. 5. A medicament for preventing or treating ebola virus infection, which is characterized in that the medicament is DCP1b siRNA for targeted inhibition of DCP1b expression; The DCP1b siRNA is siRNA-DCP1b-245 formed by annealing two single strands shown in SEQ ID NO.1 and SEQ ID NO.2, or siRNA-DCP1b-901 formed by annealing two single strands shown in SEQ ID NO.3 and SEQ ID NO.4, or siRNA-DCP1b-1833 formed by annealing two single strands shown in SEQ ID NO.5 and SEQ ID NO. 6.
6. 6. The drug of claim 1, wherein the DCP1b siRNA is siRNA-DCP1b-245 formed by annealing two single strands shown in SEQ ID No.1 and SEQ ID No. 2.

Description

Application of mRNA uncapped complex subunit protein DCP1b in preparation of medicines for preventing or treating Ebola virus infection Technical Field The invention relates to the technical field of biological medicines, in particular to application of mRNA uncapping complex subunit protein DCP1b in preparation of medicines for preventing or treating Ebola virus infection. Background Ebola Virus Disease (EVD) is a human and livestock co-borne virulent infectious disease caused by ebola virus (EBOV), which is an enveloped single-stranded negative-strand RNA virus that was discovered in 1976 to be a continuous multiple outbreak in africa, and is capable of causing acute hemorrhagic infectious disease in humans and non-human primates, with a mortality rate of about 50-90%, and the ebola virus genome sequence being 3 'end non-coding region-NP-VP 35-VP40-GP-VP30-VP24-L-5' end non-coding region, which can encode nuclear protein NP, virion protein VP35, matrix protein VP40, glycoprotein GP, VP30, VP24, RNA-dependent RNA polymerase L, together with 7 structural proteins, ebola virus, although originally targeting macrophages and dendritic cells, is ultimately capable of infecting all types of cells except lymphocytes, and currently a world problem to be effectively controlled by the current strategy. Disclosure of Invention The invention aims to solve the technical problems and provides application of mRNA uncapping complex subunit protein DCP1b in preparing medicines for preventing or treating Ebola virus infection. The invention realizes the above purpose through the following technical scheme: The invention provides an application of mRNA uncapped complex subunit protein DCP1b in preparing medicines for preventing or treating Ebola virus infection, and a substance capable of inhibiting or reducing expression of DCP1b is adopted to prepare a product for preventing or treating Ebola virus infection/proliferation or Ebola virus diseases. As a further optimization of the invention, the substances capable of inhibiting or reducing expression of DCP1b include, but are not limited to, DCP1b inhibitors, DCP1b siRNA or gene editing tools for knocking out expression of DCP1 b. As a further optimization scheme of the invention, the DCP1b siRNA is any one of siRNA-DCP1b-245, siRNA-DCP1b-901 and siRNA-DCP1 b-1833; The siRNA-DCP1b-245 is an siRNA formed by annealing two single strands shown in SEQ ID NO.1 and SEQ ID NO.2, the siRNA-DCP1b-901 is an siRNA formed by annealing two single strands shown in SEQ ID NO.3 and SEQ ID NO.4, and the siRNA-DCP1b-1833 is an siRNA formed by annealing two single strands shown in SEQ ID NO.5 and SEQ ID NO. 6; SEQ ID NO.1:5’-GGAAGGAACCUUAUUUGUUTT-3’; SEQ ID NO.2:5’-AACAAAUAAGGUUCCUUCCTT-3’; SEQ ID NO.3:5’-CAGCCAUUCAGAAACUCAUTT-3’; SEQ ID NO.4:5’-AUGAGUUUCUGAAUGGCUGTT-3’; SEQ ID NO.5:5’-GCCUAUCUCUUCAGCAUGATT-3’; SEQ ID NO.6:5’-UCAUGCUGAAGAGAUAGGCTT-3’。 as a further optimization scheme of the invention, the DCP1b siRNA is siRNA-DCP1b-245 formed by annealing two single strands shown in SEQ ID NO.1 and SEQ ID NO. 2. The invention also provides a medicine in medicines for preventing or treating Ebola virus infection, wherein the medicine is DCP1b siRNA for targeted inhibition of DCP1b expression; The DCP1b siRNA is siRNA-DCP1b-245 formed by annealing two single strands shown in SEQ ID NO.1 and SEQ ID NO.2, or siRNA-DCP1b-901 formed by annealing two single strands shown in SEQ ID NO.3 and SEQ ID NO.4, or siRNA-DCP1b-1833 formed by annealing two single strands shown in SEQ ID NO.5 and SEQ ID NO. 6. As a further optimization scheme of the invention, the DCP1b siRNA is siRNA-DCP1b-245 formed by annealing two single strands shown in SEQ ID NO.1 and SEQ ID NO. 2. The invention has the beneficial effects that: 1) The invention provides a new target for treating ebola virus disease, namely mRNA uncapping complex subunit protein DCP1b, researches show that after treatment by using mRNA uncapping complex subunit protein DCP1b siRNA (DCP 1b siRNA is siRNA-DCP1b-245, siRNA-DCP1b-901 or siRNA-DCP1 b-1833), the ebola virus replication is obviously reduced, the proliferation of ebola virus in cells is effectively inhibited, and DCP1b is expected to become a potential treatment target for ebola virus infection, the invention provides a new strategy for preventing and treating acute infectious diseases caused by ebola virus infection, and has important application value in aspects of drug development and vaccine development; 2) The invention further screens out siRNA with obvious knocking-down effect of DCP1b, namely siRNA-DCP1b-245 formed by annealing two single chains shown in SEQ ID NO.1 and SEQ ID NO.2, the siRNA has better effect of inhibiting proliferation of Ebola virus, and the invention provides a new strategy for preventing and treating acute infectious diseases caused by Ebola virus infection and has important application value in aspects of drug research and development and vaccine development. Drawings