De Francesco Raffaele, Carfí Andrea
Istituto di Ricerche di Biologia Molecolare, P. Angeletti, Via Pontina Km 30,600, 00040 Pomezia (Rome), Italy.
Adv Drug Deliv Rev. 2007 Oct 10;59(12):1242-62. doi: 10.1016/j.addr.2007.04.016. Epub 2007 Aug 11.
The HCV NS3 protease and NS5B polymerase play essential roles in the replication of the hepatitis C virus (HCV). Following the successful paradigm established for HIV protease and reverse transcriptase inhibitors, these enzymes have been elected as targets for the development of small molecule HCV inhibitors. By combining the power of high-throughput screening with rational, knowledge-based drug discovery, a number of competitive inhibitors of the NS3 protease as well as nucleoside and non-nucleoside inhibitors of the NS5B polymerase have been identified and some have now entered clinical trials. In this article we review recent progress in the discovery and development of small molecule inhibitors of these two essential viral enzymes as they are advancing in the clinic.
丙型肝炎病毒（HCV）的NS3蛋白酶和NS5B聚合酶在丙肝病毒复制过程中发挥着关键作用。继针对HIV蛋白酶和逆转录酶抑制剂所确立的成功范例之后，这些酶已被选定为开发小分子HCV抑制剂的靶点。通过将高通量筛选的强大功能与基于知识的合理药物研发相结合，现已鉴定出多种NS3蛋白酶竞争性抑制剂以及NS5B聚合酶的核苷类和非核苷类抑制剂，其中一些已进入临床试验阶段。在本文中，我们综述了这两种重要病毒酶的小分子抑制剂在临床推进过程中的发现与开发方面的最新进展。
