Viral protease inhibitors.
Viral protease inhibitors.
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DOI：
10.1007/978-3-540-79086-0_4
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发表时间：
2009
影响因子：
--
通讯作者：
Swanstrom R
中科院分区：
文献类型：
--
作者：
Anderson J;Schiffer C;Lee SK;Swanstrom R
本文综述了病毒蛋白水解酶抑制剂作为抗病毒药物的研究进展。我们专注于HIV-1蛋白酶抑制剂，因为这些药物在最近取得了最重大的进展。因此，我们讨论了HIV-1蛋白水解酶的生物化学，抑制剂的发展，抑制剂的临床应用，以及耐药性的演变。由于许多不同的病毒编码必需的蛋白酶，如果加工位点序列和催化机制已知，就有可能开发出对其他病毒有效的蛋白酶抑制剂。目前，对开发抑制剂的兴趣仅限于导致慢性病的病毒、有可能导致大规模流行的病毒，或者足够普遍的病毒，即使感染最终是自限性的，治疗急性感染也是有益的。丙型肝炎病毒蛋白水解酶抑制剂的研究进展最快，我们还对丙型肝炎病毒NS3/4A丝氨酸蛋白酶抑制剂的研究进展进行了综述，包括联合治疗和耐药。最后，我们讨论了其他作为潜在药物靶点的病毒蛋白，包括来自登革病毒、巨细胞病毒、鼻病毒和冠状病毒的那些。
This review provides an overview of the development of viral protease inhibitors as antiviral drugs. We concentrate on HIV-1 protease inhibitors, as these have made the most significant advances in the recent past. Thus, we discuss the biochemistry of HIV-1 protease, inhibitor development, clinical use of inhibitors, and evolution of resistance. Since many different viruses encode essential proteases, it is possible to envision the development of a potent protease inhibitor for other viruses if the processing site sequence and the catalytic mechanism are known. At this time, interest in developing inhibitors is limited to viruses that cause chronic disease, viruses that have the potential to cause large-scale epidemics, or viruses that are sufficiently ubiquitous that treating an acute infection would be beneficial even if the infection was ultimately self-limiting. Protease inhibitor development is most advanced for hepatitis C virus (HCV), and we also provide a review of HCV NS3/4A serine protease inhibitor development, including combination therapy and resistance. Finally, we discuss other viral proteases as potential drug targets, including those from Dengue virus, cytomegalovirus, rhinovirus, and coronavirus.