蜱传脑炎病毒非结构蛋白NS2B-NS3与NS5的研究进展

Research progress in non-structural proteins NS2B-NS3 and NS5 of tick-borne encephalitis virus

摘要:

蜱传脑炎病毒是引起严重的中枢神经系统疾病蜱传脑炎的病原体,每年在欧洲、俄罗斯远东地区、日本和中国北部报道的蜱传脑炎病例数约为10 000‒12 000例,且在我国和多个欧洲国家的发病率逐渐增高,正成为人类健康的潜在危害。主动免疫是预防蜱传脑炎的有效措施,包括我国在内的多个国家已研制出安全性较高的疫苗,但在我国流行省份的疫苗接种较为有限,特异性抗病毒药物的研发或许是治疗蜱传脑炎病毒感染的研究方向之一。蜱传脑炎病毒非结构蛋白NS2B-NS3与NS5因为在病毒基因组复制、加帽和宿主免疫调节中的重要作用,成为关键的抗病毒药物研发靶点。本文综述了蜱传脑炎病毒非结构蛋白NS2B-NS3与NS5的三维结构和抑制剂研发工作,为深入探究该病毒感染的分子机制和抗病毒药物研发提供参考。

Abstract:

Tick-borne encephalitis virus is the pathogen of tick-borne encephalitis, which causes severe central nervous system symptoms. The number of tick-borne encephalitis cases reported annually in Europe, Russian Far East, Japan, and northern China reaches 10 000- 12 000, and the incidence is gradually increasing in China and several European countries. This disease is becoming a potential hazard to human. Active immunization is an effective measure to prevent infection, and vaccines with high safety have been developed in multiple countries including China. However, the vaccination is limited in the provinces where tick-borne encephalitis is popular. The design of specific antivirals may be a feasible way for the treatment of this disease. The non-structural proteins NS2B-NS3 and NS5 of tick-borne encephalitis virus play key roles in viral genome replication, capping, and host immunomodulation, thus becoming key targets for antiviral development. In this review, we outlined the three-dimensional structures and the development of inhibitors of NS2B-NS3 and NS5 of tick-borne encephalitis virus. This review provides a reference for probing into the molecular mechanism of tick-borne encephalitis virus infection and the development of antivirals.