Massachusetts General Hospital, Department of Medicine, Gastrointestinal Unit, Boston, USA.
Gastroenterology. 2012 May;142(6):1340-1350.e1. doi: 10.1053/j.gastro.2012.02.015.
Development of robust cell culture models for hepatitis C viral infection has greatly increased our understanding of this virus and its life cycle. This knowledge has led to the development of many drugs that target specific elements of viral replication, including viral proteins and host factors required for replication. The NS3/4A serine protease inhibitors were the first of these to be used in the clinic, and reagents that target other elements of the viral lifecycle are in advanced stages of clinical development. These include new NS3/4A protease inhibitors, NS5B RNA-dependent RNA polymerase inhibitors, NS5A inhibitors, and host-directed antivirals, such as cyclophilin inhibitors. Alternative interferons with possibly improved tolerability, specifically interferon-λ1 (interleukin-29), are also under development. These new reagents against hepatitis C virus should lead to highly effective, well-tolerated, and likely interferon-sparing therapies in the next several years.
开发稳健的细胞培养模型用于丙型肝炎病毒感染，极大地增进了我们对该病毒及其生命周期的了解。这些知识促成了许多针对病毒复制特定要素（包括病毒蛋白和复制所需的宿主因子）的药物的研发。NS3/4A 丝氨酸蛋白酶抑制剂是最早在临床上应用的药物，而针对病毒生命周期其他要素的试剂已处于临床开发的后期阶段。这些试剂包括新型 NS3/4A 蛋白酶抑制剂、NS5B RNA 依赖性 RNA 聚合酶抑制剂、NS5A 抑制剂和宿主导向型抗病毒药物，如亲环素抑制剂。具有可能改善耐受性的替代干扰素，特别是干扰素-λ1（白细胞介素-29），也正在研发中。在未来几年，这些针对丙型肝炎病毒的新型试剂有望带来高效、耐受良好且可能无需干扰素的治疗方法。
