Belon Craig A, Frick David N
New York Medical College, Department of Biochemistry & Molecular Biology, Valhalla, NY 10595, USA, Tel.: +1 914 594 3537; ;
Future Virol. 2009 May 1;4(3):277-293. doi: 10.2217/fvl.09.7.
The hepatitis C virus (HCV) leads to chronic liver disease and affects more than 2% of the world's population. Complications of the disease include fibrosis, cirrhosis and hepatocellular carcinoma. Current therapy for chronic HCV infection, a combination of ribavirin and pegylated IFN-alpha, is expensive, causes profound side effects and is only moderately effective against several common HCV strains. Specifically targeted antiviral therapy for hepatitis C (STAT-C) will probably supplement or replace present therapies. Leading compounds for STAT-C target the HCV nonstructural (NS)5B polymerase and NS3 protease, however, owing to the constant threat of viral resistance, other targets must be continually developed. One such underdeveloped target is the helicase domain of the HCV NS3 protein. The HCV helicase uses energy derived from ATP hydrolysis to separate based-paired RNA or DNA. This article discusses unique features of the HCV helicase, recently discovered compounds that inhibit HCV helicase catalyzed reactions and HCV cellular replication, and new methods to monitor helicase action in a high-throughput format.
丙型肝炎病毒（HCV）可导致慢性肝病，全球超过2%的人口受其影响。该疾病的并发症包括纤维化、肝硬化和肝细胞癌。目前针对慢性HCV感染的治疗方法是利巴韦林和聚乙二醇化干扰素-α联合使用，这种方法费用高昂，会引起严重的副作用，而且对几种常见的HCV毒株效果一般。丙型肝炎特异性靶向抗病毒治疗（STAT-C）可能会补充或取代现有治疗方法。STAT-C的主要化合物靶向HCV非结构（NS）5B聚合酶和NS3蛋白酶，然而，由于病毒耐药性的持续威胁，必须不断开发其他靶点。HCV NS3蛋白的解旋酶结构域就是这样一个尚未充分开发的靶点。HCV解旋酶利用ATP水解产生的能量来分离碱基配对的RNA或DNA。本文讨论了HCV解旋酶的独特特征、最近发现的抑制HCV解旋酶催化反应和HCV细胞复制的化合物，以及以高通量形式监测解旋酶作用的新方法。
