Lu Lu, Yu Fei, Cai Lifeng, Debnath Asim K, Jiang Shibo
Key Laboratory of Medical Molecular Virology of MOE/MOH, Shanghai Medical College, Fudan University, 130 Dong An Road, Building #13, Shanghai 200032, China.
Curr Top Med Chem. 2016;16(10):1074-90. doi: 10.2174/1568026615666150901114527.
Human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein surface subunit gp120 and transmembrane subunit gp41 play important roles in HIV-1 entry, thus serving as key targets for the development of HIV-1 entry inhibitors. T20 peptide (enfuvirtide) is the first U.S. FDA-approved HIV entry inhibitor; however, its clinical application is limited by the lack of oral availability. Here, we have described the structure and function of the HIV-1 gp120 and gp41 subunits and reviewed advancements in the development of small-molecule HIV entry inhibitors specifically targeting these two Env glycoproteins. We then compared the advantages and disadvantages of different categories of HIV entry inhibitor candidates and further predicted the future trend of HIV entry inhibitor development.
人类免疫缺陷病毒1型（HIV-1）包膜（Env）糖蛋白表面亚基gp120和跨膜亚基gp41在HIV-1进入过程中发挥重要作用，因此成为开发HIV-1进入抑制剂的关键靶点。T20肽（恩夫韦肽）是美国食品药品监督管理局（FDA）批准的首个HIV进入抑制剂；然而，其临床应用因缺乏口服可用性而受到限制。在此，我们描述了HIV-1 gp120和gp41亚基的结构与功能，并综述了特异性靶向这两种Env糖蛋白的小分子HIV进入抑制剂的研发进展。然后，我们比较了不同类别HIV进入抑制剂候选物的优缺点，并进一步预测了HIV进入抑制剂的未来发展趋势。
