Shi Wei-guo, Jia Qi-yan, Liu Ke-liang
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
Yao Xue Xue Bao. 2010 Feb;45(2):184-93.
HIV-1 fusion inhibitors are a new class of anti-HIV compounds, which block the entry of HIV into target cells through preventing the fusion between viral and cell plasma membrane and thus interrupt the initial steps of viral replication. T-20 (enfuvirtide), which has been clinically approved as the first fusion inhibitor of HIV-1 by U.S. FDA in 2003, can suppress replication of HIV variants with multi-drug resistance to reverse transcriptase and protease inhibitors. Peptides and small molecules display potent anti-HIV fusion activities by targeting gp41 thus inhibit its fusogenic function. In recent years, with the development of studies on the molecular mechanism of HIV membrane fusion process and the function of gp41, many new fusion inhibitors are found and some have been in advanced clinical trials. This review discusses recent progress in the development of HIV-1 fusion inhibitors targeting the gp41.
HIV-1融合抑制剂是一类新型抗HIV化合物，其通过阻止病毒与细胞质膜融合来阻断HIV进入靶细胞，从而中断病毒复制的初始步骤。T-20（恩夫韦肽）于2003年被美国食品药品监督管理局临床批准为首个HIV-1融合抑制剂，它能够抑制对逆转录酶和蛋白酶抑制剂具有多重耐药性的HIV变体的复制。肽类和小分子通过靶向gp41显示出强大的抗HIV融合活性，从而抑制其融合功能。近年来，随着对HIV膜融合过程分子机制及gp41功能研究的进展，发现了许多新型融合抑制剂，其中一些已进入临床试验后期。本文综述了靶向gp41的HIV-1融合抑制剂的最新研究进展。
