基于丙型肝炎病毒非结构蛋白NS5B晶体结构的抑制剂筛选

丙型肝炎病毒（hepatitis C virus，HCV）是引起慢性肝炎的主要病原体之一，主要通过血源传播，严重危害人类的健康，寻找有效的抗病毒药物具有重要意义。随着HCV复制过程中一些重要蛋白以及这些蛋白与相关配体或抑制剂的精确三维结构的解析，对这些蛋白的三维结构进行设计和筛选，成为目前开发治疗HCV感染药物的重要手段。NS5BRNA聚合酶是HCV复制过程中的关键酶，是研究抗HCV病毒药物的一个重要靶点。本文以NS5B的晶体结构为基础，用晶体浸泡的方法进行NS5B蛋白的抑制剂筛选，得到了小分子抑制剂与NS5B蛋白的精确三维结构，从原子水平上阐释了抑制剂对HCVNS5B蛋白的抑制机理。

Fragment = based discovery of hepatitis C virus non - structure NS5B polymerase inhibitors

Hepatitis C virus （ HCV } , one of the main pathogens that cause chronic hepatitis, mainly spreads through the blood source and does harm to human health severely. It is very necessary to look for an effective antiviral drug. With the precise three - dimensional structure analysis of some important proteins in the course of HCV replication, these proteins and related ligands or in- hibitors were designed, designing and screening drugs against HCV infection based on the structural analysis of these proteins has become an important method for the development of therapeutic HCV drugs. A viral protein, HCV NS5B RNA polymerase, is the key enzyme involved in the replication of the HCV gene and has been one of the main targets for drug development. Beginning with crystallographic fragment screening, inhibitors of HCV NSSb RNA polymerase were discovered by a fragment - based lead discovery method. This research presents the structures of inhibitors bound non -covalently to NSSB, and explains the inhibitory mechanism to HCV NS5 B protein at the level of atoms.