CN-122005797-A - Application of neuropilin 2 in preparation of medicines for preventing and treating chikungunya virus infection

Abstract

The invention relates to the technical field of biomedicine, in particular to a novel target spot for resisting chikungunya virus infection and application thereof. The invention takes human neuroblastoma cells (SH-SY 5Y) and human brain astrocyte tumor cells (U87) as target cells, adopts RNA interference technology to down regulate the expression of receptor acting membrane proteins of target cell parts, searches host factors capable of effectively inhibiting CHIKV from infecting human nerve cells, and achieves the aim of blocking CHIKV infection from the source. The invention discovers that the neuropilin 2 (NRP 2) plays an important role in the infection of SH-SY5Y and U87 cells by CHIKV, down regulates the expression of the NRP2 and can obviously inhibit the infection of the CHIKV. The invention provides application of NRP2 in preparing medicines for preventing or treating chikungunya virus infection, and provides a new target point and a new treatment scheme for clinically preventing and treating diseases such as fever, arthralgia, joint swelling, muscle pain, headache, nausea, fatigue, rash and the like caused by chiKV infection.

Inventors

• DING CUILING
• CHEN YIBEI
• ZHAO PING
• QI ZHONGTIAN
• HE YANHUA
• HE ZHIWEI
• TANG HAILIN

Assignees

• 中国人民解放军海军军医大学

Dates

Publication Date

20260512

Application Date

20251031

Claims (7)

1. 1. Application of neuropilin 2 in preparing medicines for preventing or treating chikungunya virus infection is provided.
2. 2. The use of neuropilin 2 according to claim 1 for the manufacture of a medicament for the prevention or treatment of chikungunya virus infection, wherein said use of neuropilin 2 for the manufacture of a medicament for the prevention or treatment of fever, arthritis, joint pain, joint swelling, muscle pain, headache, nausea, fatigue and rash caused by chikungunya virus infection.
3. 3. The use of neuropilin 2 according to claim 1 for the preparation of a medicament for preventing or treating infection by chikungunya virus, wherein said medicament is a medicament for inhibiting infection by chikungunya virus by inhibiting or down-regulating the expression level of neuropilin 2.
4. 4. Use of an agent that inhibits or down regulates an expression level of neuropilin 2 in the preparation of a medicament for preventing or treating chikungunya virus infection.
5. 5. The use of an agent for inhibiting or down-regulating the expression level of neuropilin 2 according to claim 4, in the preparation of a medicament for preventing or treating chikungunya virus infection, wherein said agent for inhibiting or down-regulating the expression level of neuropilin 2 is a siRNA, shRNA, miRNA or antisense nucleotide or a recombinant vector comprising siRNA, shRNA, miRNA or antisense nucleotide which specifically interferes with the expression, processing of the neuropilin 2 gene.
6. 6. The use of an agent for inhibiting or down-regulating the expression level of neuropilin 2 according to claim 4, wherein said agent for inhibiting or down-regulating the expression level of neuropilin 2 is an interfering RNA of neuropilin 2, the nucleotide sequence of said interfering RNA being shown in any one of SEQ ID No. 1, SEQ ID No. 2, and SEQ ID No. 3.
7. 7. A medicament for preventing or treating chikungunya virus infection, comprising an agent which inhibits or down-regulates the expression level of neuropilin 2.

Description

Application of neuropilin 2 in preparation of medicines for preventing and treating chikungunya virus infection Technical Field The invention relates to the technical field of biomedicine, in particular to a novel target spot for resisting chikungunya virus infection and application thereof. Background Chikungunya fever (Chikungunya fever, CHIKF) is an arboinfectious disease caused by chikungunya virus (Chikungunya virus, CHIKV) infection, and typical clinical manifestations include fever, rash, arthralgia, myalgia, and the like. CHIKV belongs to the togaviridae family, genus alphavirus. The virus particles are spherical, 65nm in diameter and enveloped. The acute phase of CHIKV infection is mainly characterized by persistent hyperthermia, with significant viremia and strong innate immune responses, which can last for up to a week. After the fever symptoms appear, most patients develop severe bilateral symmetry multi-joint pain, and lesions mainly involve distal joints such as wrist joints and ankle joints and hand facet joints. Although viremia usually clears 8 days after infection and most acute symptoms subside within 1 month, epidemiological studies have shown that some individuals develop persistent arthritis and arthralgia symptoms, which can last from months to years, wherein patients who incorporate underlying chronic disease are more prone to develop chronic disease processes, greatly affecting the quality of life of the patient, and imposing a significant economic burden thereon. However, no specific and efficient antiviral drugs and effective vaccines are approved for clinical application in CHIKV at present, and most patients are still symptomatic treatment mainly due to limited understanding of CHIKV pathogenesis, and various factors may play important roles in the infection process. Matrix remodeling associated protein 8 (matrix remodeling associated, mxra 8) is currently widely recognized as a receptor for a variety of arthritic alphaviruses including CHIKV. However, there are other host factors that can play a critical role in the CHIKV infection process, for example, overexpression of the T cell immunoglobulin and mucin domain (T-cell immunoglobin and mucin domain protein-1, tim-1) in HEK293T cells can significantly enhance CHIKV virion binding and endocytosis. The CO-IP experiment, the siRNA knockdown experiment and the antibody blocking experiment all prove that inhibin (PHB) can influence the infection of the chiKV to host cells. In recent years, FHL1 is found to be a key host factor required for CHIKV infection through whole genome CRISPR-Cas9 screening, but knockout of FHL1A can significantly promote infection of CHIKV and ONNV, and FHL1 plays a key role mainly in the CHIKV replication stage. Therefore, screening host factors capable of affecting virus infection can provide a basis for research on the pathogenic mechanism of CHIKV and research on specific antiviral drugs. Neuropilin (Neuropilins, NRPs) is a non-tyrosine kinase transmembrane receptor protein whose gene sequence is well conserved in all vertebrates. As a receptor for neurite-directing factor signaling, neuropilin not only regulates neural development, but also interacts with VEGF, mediating development of blood and lymphatic vessels. NRPs include two subtypes, neuropilin 1 (NRP 1) and neuropilin 2 (NRP 2), which can form homodimers and heterodimers and are highly conserved in vertebrates. There have been studies showing that both NRP2 and NRP1 act as receptors to affect infection with the novel coronavirus (SARS-CoV-2). In addition, NRP2 is also a receptor for human cytomegalovirus (human cytomegalovirus, HCMV), rabies virus (Rabies virus, RABV), and ruabout virus (Lujo virus, LUJV). However, no report about the role of the NRP2 molecule in the infection of host cells by the CHIKV virus exists at present, and the intensive research on the NRP2 molecule not only can promote the knowledge of the infection and pathogenic mechanism of the CHIKV, but also can provide a new thought and target for preventing and treating the infection of the CHIKV. Disclosure of Invention The invention aims to provide a novel target for resisting chikungunya virus infection, namely neuropilin 2 (Neuropilin-2, NRP 2). It is a further object of the present invention to provide novel uses of neuropilin 2 (NRP 2) molecules, in particular in combating chikungunya virus infection. A third object of the present invention is to provide siRNA that interferes with expression of a neuropilin 2 (NRP 2) molecule and uses thereof. In order to achieve the above purpose, the main technical scheme of the invention is as follows: According to the invention, human neuroblastoma cells (SH-SY 5Y) and human brain astroblastoma cells (U87) are used as target cells, and an RNA interference technology is adopted to down regulate the expression of receptor acting membrane proteins of the target cells, so that host factors capable of effectively inhibiting CHIKV infection