Horscroft Nigel, Lai Vicky C H, Cheney Wayne, Yao Nanhua, Wu Jim Z, Hong Zhi, Zhong Weidong
Drug Discovery, Valeant Pharmaceuticals International, Costa Mesa, CA, USA.
Antivir Chem Chemother. 2005;16(1):1-12. doi: 10.1177/095632020501600101.
Discovery of potential therapeutics against hepatitis C virus (HCV) infection has been hampered in the past decade by the inability to grow this virus in tissue culture and by the lack of robust small animal models. This situation has been improved by the recent development of a selectable HCV replicon cell culture system. For the first time, drug discovery scientists are able to screen large compound collections using the replicon cell culture system to identify small molecules with the potential to inhibit HCV RNA replication. The replicon system has also been used to elucidate inhibitors' antiviral mechanism of action and to optimize antiviral potency. In this review, we will summarize the recent development of HCV replicon cell culture system and its use in anti-HCV drug discovery. The antiviral activities of promising lead compounds are also reviewed.
在过去十年中，丙型肝炎病毒（HCV）感染潜在治疗药物的研发受到阻碍，原因在于无法在组织培养中培养该病毒，且缺乏可靠的小动物模型。最近可选择的HCV复制子细胞培养系统的开发改善了这种情况。药物研发科学家首次能够使用复制子细胞培养系统筛选大量化合物库，以鉴定具有抑制HCV RNA复制潜力的小分子。复制子系统也已用于阐明抑制剂的抗病毒作用机制并优化抗病毒效力。在本综述中，我们将总结HCV复制子细胞培养系统的最新进展及其在抗HCV药物研发中的应用。还将综述有前景的先导化合物的抗病毒活性。
