丙型肝炎病毒NS5B RNA聚合酶抑制剂研究进展

摘要

丙型肝炎病毒(hepatitis C virus,HCV)是引起慢性肝炎并进而发展为肝硬化和肝细胞癌的主要病原体之一.目前,临床上采用a-干扰素(IFN-α)和利巴韦林(RBV)联合用药治疗丙型肝炎,但有效率仅为40％～50％.寻找HCV特定靶向抗病毒治疗药物是抗HCV研究的重要方向,相应靶点包括NS2和NS3蛋白酶,NS4A、NS4B、NS5A和NS5B,其中以NS5B RNA依赖性RNA聚合酶(NS5B RdRp)为靶标的抗HCV药物研究近年来颇受关注.本文在介绍NS5B及NS5B RdRp结构和功能的基础上,总结归纳以NS5B RdRp为靶点的HCV特定靶向抗病毒治疗药物研究的主要策略,以及近年来相关NS5BRdRp抑制剂的研究进展.%Hepatitis C virus (HCV) is one of the major causative pathogens of chronic hepatitis which may lead to liver cirrhosis and hepatocellular carcinoma. Currently, the standard treatment for HCV is the combination of pegylated interferon-α (IFN-α)plus ribavirin. Unfortunately, this treatment does not show lasting improvement in 50%-60% of the patients and has many disadvantages such as long treatment period, high cost and undesirable side effects. Exploring novel specifically targeted antiviral therapy for HCV(STAT-C) has been the important direction in the anti-HCV research area, and many anti-HCV targets have been found, such as NS2 and NS3 proteases,NS4A,NS4B,NS5A and NS5B RNA-dependent RNA polymerase (NS5B RdRp). In recent years, developing novel anti-HCV drugs to target NS5B RdRp has become one of important strategies. This review highlights the structure and function of NS5B RdRp, the main strategies targeting NS5B RdRp and the recent advances in its inhibitors.