以gp120、CD4和CXCR4为靶点的HIV小分子进入抑制剂研究进展

摘要

艾滋病是由人类免疫缺陷病毒(HIV)引起的一种烈性传染病,危害极大.病毒的包膜蛋白gp120及其受体CD4、辅助受体CXCR4在病毒感染中起着重要的作用.其中,gp120的Phe43口袋结构和Arg59是其与CD4分子相互作用的重要部位.HIV小分子进入抑制剂因能在HIV感染细胞前即发挥抑制病毒的作用,成为近年来抗HIV药物研究的热点.Phe43口袋结构是小分子进入抑制剂的重要靶点,目前研究热点化合物主要有BMS-378806、BMS-488043及其类似物、NBD-556及其类似物.靶向CXCR4也是研究HIV小分子进入抑制剂的一个重要方向.%AIDS is an infectious disease caused by human immunodeficiency virus(HIV)and has done great harm to human beings. The envelope glycoprotein surface subunit gp120 and its receptor CD4 and coreceptor CXCR4 play important roles in HIV-1 en?try. The Phe43 pocket and Arg59 of gp120 are two important regions that interact with CD4. Recently,HIV small-molecule entry inhib?itors have become a hot topic in anti-HIV drug research,which are able to inhibit the virus before the cells are infected. The Phe43 pocket is an attractive target and the study of Phe43 pocket-targeting small-molecule entry inhibitors is underway,including BMS-378806,BHS-488043 and its analogs,and NBD-556 and its analogs. Besides,CXCR4 antagonist is another important approach.