Department of Virology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
Curr Top Microbiol Immunol. 2013;369:321-42. doi: 10.1007/978-3-642-27340-7_13.
Resolution of the three-dimensional structures of several Hepatitis C virus (HCV) proteins, together with the development of replicative cell culture systems, has led to the identification of a number of potential targets for direct-acting antiviral agents (DAA). Numerous families of drugs that potently inhibit the HCV life cycle in vitro have been identified, and some of these molecules have reached early to late clinical development. Two NS3-4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with pegylated interferon (IFN)-α and ribavirin for the treatment of chronic hepatitis C related to HCV genotype 1. A number of other DAAs are at the clinical developmental stage in combination with pegylated IFN-α and ribavirin or with other DAAs in IFN-free regimens, with or without ribavirin. They include second-wave, first-generation, and second-generation NS3-4A protease inhibitors, nucleoside/nucleotide analogue inhibitors, and non-nucleoside inhibitors of HCV RNA-dependent RNA polymerase, inhibitors of nonstructural protein 5A and host-targeted agents, such as cyclophilin A inhibitors and microRNA-122 antagonists. The proof of concept that IFN-free regimens can lead to HCV eradication has recently been brought. This chapter provides an overview of the current treatment of HCV infection and discusses the future of HCV therapy with new anti-HCV drugs.
几种丙型肝炎病毒（HCV）蛋白的三维结构的解析，以及复制细胞培养系统的发展，导致了一些直接作用抗病毒药物（DAA）的潜在靶标的确定。已经鉴定出了许多在体外能强烈抑制 HCV 生命周期的药物家族，其中一些分子已经进入早期到晚期临床开发阶段。两种 NS3-4A 蛋白酶抑制剂，telaprevir 和 boceprevir，于 2011 年在欧洲和美国获得批准，与聚乙二醇化干扰素（IFN）-α和利巴韦林联合用于治疗与 HCV 基因型 1 相关的慢性丙型肝炎。许多其他的 DAA 与聚乙二醇化 IFN-α和利巴韦林联合，或与无 IFN 的方案中的其他 DAA 联合，无论是否有利巴韦林，都处于临床开发阶段。它们包括第二代、第一代和第二代 NS3-4A 蛋白酶抑制剂、核苷/核苷酸类似物抑制剂、HCV RNA 依赖性 RNA 聚合酶的非核苷抑制剂、非结构蛋白 5A 的抑制剂和宿主靶向剂，如亲环素 A 抑制剂和 microRNA-122 拮抗剂。最近已经证明了无 IFN 方案可以导致 HCV 清除的概念。本章概述了目前 HCV 感染的治疗方法，并讨论了新的抗 HCV 药物对 HCV 治疗的未来。
