Tsai Ching-Hsiu, Lee Pei-Yu, Stollar Victor, Li Mei-Ling
Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan.
Curr Pharm Des. 2006;12(11):1339-55. doi: 10.2174/138161206776361156.
Viral DNA and RNA polymerases are enzymes, which are responsible for copying the genetic materials of viruses and are therefore central components in the life cycles of viruses. The polymerases are essentially required for the replication of viruses. The reverse transcriptase (RT) of the retroviruses and the hepadnaviruses is the sole viral enzyme required for the synthesis of DNA from viral RNA. Viral polymerases are therefore an extremely favorable target for the development of antiviral therapy. The success of anti-HIV-1 therapy using inhibitors specifically targeting HIV RT suggests that other viral polymerases can be the valid molecular targets for the design of antiviral drugs. Intensive structural and functional studies of viral polymerases have been conducted and have opened new avenues for the development of more effective antiviral therapy. This review summarizes the insights gained from recent structural and functional studies of antiviral agents, which target viral polymerases. The primary focus will be on hepatitis C virus (HCV), herpesviruses, HIV, hepatitis B virus (HBV) and influenza virus.
病毒DNA和RNA聚合酶是负责复制病毒遗传物质的酶，因此是病毒生命周期的核心组成部分。聚合酶对于病毒复制至关重要。逆转录病毒和嗜肝DNA病毒的逆转录酶（RT）是从病毒RNA合成DNA所需的唯一病毒酶。因此，病毒聚合酶是抗病毒治疗开发的一个极其理想的靶点。使用特异性靶向HIV RT的抑制剂进行抗HIV-1治疗的成功表明，其他病毒聚合酶可以成为设计抗病毒药物的有效分子靶点。已经对病毒聚合酶进行了深入的结构和功能研究，为开发更有效的抗病毒治疗开辟了新途径。本综述总结了从近期针对病毒聚合酶的抗病毒药物的结构和功能研究中获得的见解。主要重点将放在丙型肝炎病毒（HCV）、疱疹病毒、HIV、乙型肝炎病毒（HBV）和流感病毒上。
