丙型肝炎病毒NS3-4A蛋白酶靶向抗病毒治疗及耐药研究进展

Advances in antiviral therapy targeting to hepatitis C virus NS3/4A protease

丙型肝炎病毒（HCV）基因组的高度变异性使得HCV感染易呈慢性化,并极大地增加了肝硬化和肝癌的发病风险.效仿HIV蛋白酶抑制剂临床应用中取得的巨大成功,NS34A丝氨酸蛋白酶成为抗HCV感染小分子药物研发的重要靶点.此文围绕HCV NS3-4A蛋白酶抑制剂研发的最新进展、抗病毒活性、药代动力学特性、不良反应及抗药性突变进行了综述.

Hepatitis C virus （HCV） genome is of high variation,which results in persistent infection of HCV and increases the incidence of liver cirrhosis and hepatocellular carcinoma.Following the successful paradigm established for HIV protease inhibitors,HCV NS3-4A serine protease has been selected as the main target for the development of small molecule antiviral agents.In this article,we review recent progress in the discovery and development of HCV NS3-4A protease inhibitors,and discuss their antiviral activities,pharmacokinetic properties,side effects and resistance profiles.