Department of Medical Microbiology &Immunology, 6-020K Katz Group Centre, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada.
Toronto Centre for Liver Disease, University Health Network, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, M5C 2C4, Canada.
Nat Rev Gastroenterol Hepatol. 2016 Jun;13(6):338-51. doi: 10.1038/nrgastro.2016.60. Epub 2016 May 5.
The treatment of HCV infection has evolved at an extremely rapid pace over the past few years. The development of direct-acting antiviral agents, which potently inhibit different stages in the viral life cycle, has led to the replacement of interferon with well-tolerated oral therapies with cure rates of >90% in most patient populations. Understanding the mechanisms of action of the various agents as well as related issues, including the molecular basis for resistance, helps to guide drug development and clinical use. In this Review, we provide a mechanistic description of NS3/4A protease inhibitors, nucleotide and non-nucleotide inhibitors of the NS5B viral polymerase and inhibitors of the NS5A protein, followed by a summary of clinical data from studies of each drug class alone and in combination. Remaining challenges in drug development efforts are also discussed.
在过去的几年中，HCV 感染的治疗取得了飞速的发展。直接作用抗病毒药物的发展，强力抑制病毒生命周期的不同阶段，已经导致干扰素被大多数患者人群中耐受性良好的口服治疗药物所取代，治愈率超过 90%。了解各种药物的作用机制以及相关问题，包括耐药的分子基础，有助于指导药物开发和临床应用。在这篇综述中，我们提供了 NS3/4A 蛋白酶抑制剂、NS5B 病毒聚合酶的核苷酸和非核苷酸抑制剂以及 NS5A 蛋白抑制剂的机制描述，随后总结了每种药物单独和联合使用的临床数据。还讨论了药物开发工作中的其他挑战。
