Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Iranian Comprehensive Hemophilia Care Center, Tehran, Iran.
Curr Pharm Des. 2020;26(34):4304-4314. doi: 10.2174/1381612826666200509233215.
Many studies have been performed to develop an antiviral therapy against the hepatitis C virus (HCV) infections. The usual treatment for HCV infection is a combination of PEGylated interferon and ribavirin which offer restricted efficiency and major side effects. Thus, recent development in molecular biology of HCV and its life cycle led to the design of many drugs that target viral proteins and host factors required for viral replication. These drugs were named as direct-acting antivirals (DAAs) that were specifically designed for inhibition of viral life cycle, promising tolerability, short duration of treatment, higher barrier to resistance, and fewer drug interactions. The use of DAAs for the treatment of HCV infection resulted in high virological cure rates in patients. However, the use of combined DAA regimens may present drug interactions especially in patients under treatment for other co-morbidities. On the other hand, drug resistance against virus infection determines the success of long-term therapy. High genetic diversity among HCV virions due to error-prone polymerase activity led to the reduced susceptibility to DAA-therapy. Therefore, preclinical and clinical analysis of HCV resistance to novel drugs is needed. In this review, we describe pharmaceutical approaches for HCV treatment, structural and functional properties of DAAs, the principles of HCV drug-drug interaction, and finally HCV resistance to DAAs.
许多研究旨在开发针对丙型肝炎病毒 (HCV) 感染的抗病毒疗法。HCV 感染的常规治疗是聚乙二醇干扰素和利巴韦林联合治疗，其疗效有限且副作用较大。因此，近年来 HCV 的分子生物学及其生命周期的研究进展促使设计了许多针对病毒蛋白和病毒复制所需宿主因子的药物。这些药物被称为直接作用抗病毒药物 (DAA)，专门设计用于抑制病毒生命周期，具有良好的耐受性、治疗周期短、耐药屏障高和药物相互作用少等特点。DAA 用于 HCV 感染的治疗可使患者获得高病毒学治愈率。然而，联合 DAA 方案的使用可能会出现药物相互作用，尤其是在同时治疗其他合并症的患者中。另一方面，病毒耐药性决定了长期治疗的成败。由于 HCV 聚合酶的易错活性导致病毒粒子的遗传高度多样性，从而降低了对 DAA 治疗的敏感性。因此，需要对 HCV 对新型药物的耐药性进行临床前和临床分析。在这篇综述中，我们描述了 HCV 治疗的药物方法、DAA 的结构和功能特性、HCV 药物相互作用的原则以及 DAA 耐药性。
