Wang Ting, Duan Yong
Genome Center and Bioinformatics Program and Department of Applied Science, 431 East Health Science Drive, University of California, Davis, CA 95616-8816, USA.
Infect Disord Drug Targets. 2009 Jun;9(3):279-88. doi: 10.2174/1871526510909030279.
The CC-chemokine receptor 5 (CCR5), a membrane protein belonging to the G-protein coupled receptor super-family, has been identified as an essential co-receptor for HIV entry into the cells, and small molecules that inhibit HIV entry by targeting CCR5 have been in fast development as antiviral agents. This review focuses on computational studies of predicting the CCR5 structure and its interactions with known small molecule inhibitors and discusses how the recently solved GPCR structures would provide new insights into the modeling of CCR5-inhibitor binding. In addition, this review pays a particular attention to the design of the inhibitors that specifically interrupt the viral entry co-receptor activity of CCR5 while preserving its normal chemokine receptor function to minimize side effects and toxicity.
C-C趋化因子受体5（CCR5）是一种属于G蛋白偶联受体超家族的膜蛋白，已被确定为HIV进入细胞所必需的共受体，通过靶向CCR5来抑制HIV进入的小分子作为抗病毒药物正在快速发展。本文综述聚焦于预测CCR5结构及其与已知小分子抑制剂相互作用的计算研究，并讨论最近解析的GPCR结构如何为CCR5-抑制剂结合的建模提供新见解。此外，本文特别关注那些能特异性阻断CCR5的病毒进入共受体活性，同时保留其正常趋化因子受体功能以最小化副作用和毒性的抑制剂的设计。
