丙型肝炎病毒聚合酶抑制剂的研究进展

Recent progress in inhibitors against hepatitis C virus polymerase

丙型肝炎病毒(HCV)是引起慢性肝炎的主要病原体之一,临床上采用聚乙二醇干扰素和利巴韦林联合用药抗病毒治疗,但总体疗效不理想。目前以HCV编码的蛋白为靶点的直接抗病毒药物研发进展迅速,特别是HCV聚合酶抑制剂sofosbuvir的上市以及其显著的治疗效果使得近年来HCV聚合酶抑制剂的研发成为研究者们关注的重点。目前有多个临床在研究HCV聚合酶抑制剂,主要分为2类:核苷/核苷酸类似物和非核苷类似物。本文总结归纳了近年来HCV聚合酶抑制剂的临床研究进展。

Hepatitis C virus（ HCV） is one of the major causative pathogens of chronic hepatitis. Currently,the standard treatment for HCV is the combination of pegylated interferon-α plus ribavirin,but the whole efficiency is relatively low. In recent years,the research and development of direct-acting antiviral drugs which target HCV-encoded protein is in rapid progress. Especially,sofosbuvir,one of HCV polymerase inhibitors,was marketed last year and showed significant treatment effect in clinic and clinic trial,which makes HCV polymerase become the focal target in the future. Up to now,there are several HCV polymerase inhibitors in clinic trial,mainly divided into two categories,nucleoside / nucleotide analogues and non-nucleoside analogues. The structure and function of HCV polymerase were introduced and the recent progress in its inhibitors in clinic trial was reviewed.