The flavivirus protease as a target for drug discovery.
The flavivirus protease as a target for drug discovery.
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DOI：
10.1007/s12250-013-3390-x
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发表时间：
2013-12
影响因子：
5.5
通讯作者：
Li, Hongmin
中科院分区：
文献类型：
--
作者：
Brecher, Matthew;Zhang, Jing;Li, Hongmin
许多黄病毒是重要的人类病原体，在它们流行的地区引起相当大的疾病负担，包括脑炎和出血热。黄病毒感染的治疗方法的缺乏已经引起了对靶向黄病毒复制所必需的蛋白质（如病毒蛋白酶）的药物开发的兴趣。在病毒复制过程中，黄病毒基因组被翻译为单个多蛋白前体，其必须被病毒蛋白酶NS 3及其辅因子NS 2B的复合物切割成单个蛋白质。由于这种切割是病毒生命周期的一个必要步骤，黄病毒蛋白酶是抗病毒药物开发的一个有吸引力的靶标。在这篇综述中，我们将调查最近的药物开发研究针对NS 3活性位点，以及研究针对NS 2B/NS 3相互作用的网站确定从黄病毒蛋白酶晶体结构。
Many flaviviruses are significant human pathogens causing considerable disease burdens, including encephalitis and hemorrhagic fever, in the regions in which they are endemic. A paucity of treatments for flaviviral infections has driven interest in drug development targeting proteins essential to flavivirus replication, such as the viral protease. During viral replication, the flavivirus genome is translated as a single polyprotein precursor, which must be cleaved into individual proteins by a complex of the viral protease, NS3, and its cofactor, NS2B. Because this cleavage is an obligate step of the viral life-cycle, the flavivirus protease is an attractive target for antiviral drug development. In this review, we will survey recent drug development studies targeting the NS3 active site, as well as studies targeting an NS2B/NS3 interaction site determined from flavivirus protease crystal structures.