HIV进入抑制剂研究进展

Research Progress in HIV Entry Inhibitors

HIV进入抑制剂主要干预病毒包膜与靶细胞膜融合过程,可有效预防HIV感染。在HIV进入细胞过程中,HIV包膜糖蛋白gp120首先与宿主细胞膜上的CD4分子结合,使gp120构型变化,继而与CCR5或CXCR5等辅助受体结合,诱使跨膜亚基gp41构型改变,HIV包膜与细胞膜空间靠近,最终融合。基于这一过程,可通过筛选与gp120结合的化合物、设计CD4模拟物、研制CD4或CCR5单抗、构建辅助受体抑制剂等方法,从各个方面干预HIV的进入。对HIV进入抑制剂的靶标和药物研发进展进行概述。

HIV entry inhibitors can effectively prevent HIV infection mainly by interfering with the fusion process of virus envelope and cell membrane. During the entry of HIV into cells, HIV-coated glycoprotein gp120 first binds with CD4 molecules on host cell membrane to cause conformational changes of gp120. Then, the subsequent binding of gp120 with CCR5 or CXCR5 induces conformational changes of gp41, making the virus further approach and finally fuse to target cell. Strategies like screening for compounds that bind to gp120, designing CD4 mimics, developing CD4 or CCR5 monoclonal antibodies and constructing accessory receptor inhibitors have been developed to prevent viral entry. The progresses in targets of HIV entry inhibitors and new drugs R＆D have been reviewed in this paper.