针对人类免疫缺陷病毒结构蛋白Gag-Pol的抑制剂及其作用机制研究进展  

Research progress in inhibitors of structural protein Gag-Pol of human immunodeficiency virus and its mechanism

作　　者：黄国锋[1] 李聪宜 王虹[1] 张文艳[1] HUANG Guofeng;LI Congyi;WANG Hong;ZHANG Wenyan(AIDS and Virus Research Institute,Jilin University,Changchun 130021,China)

机构地区：[1]吉林大学艾滋病与病毒研究所,吉林长春130021

出　　处：《吉林大学学报（医学版）》2024年第4期1156-1163,共8页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金面上项目(82272316);吉林省科技厅分子病毒学重点实验室项目(20102209)。

摘　　要：Gag-Pol蛋白是人类免疫缺陷病毒(HIV)重要结构蛋白之一,其组成成分包含了HIV的基本骨架蛋白和生命周期中所需要的功能酶,目前以Gag-Pol上不同的功能区为靶点开发的抑制剂包括衣壳(CA)抑制剂、蛋白酶抑制剂、逆转录酶抑制剂和整合酶抑制剂等。CA抑制剂通过抑制CA的成熟或者破坏CA的组装进而影响HIV复制。蛋白酶抑制剂主要的作用机制是抑制蛋白酶对切割位点CA-间隔多肽1(SP1)的切割,逆转录酶抑制剂通过模仿逆转录底物,阻断HIV的逆转录过程,整合酶抑制剂通过靶向整合酶活性中心—锌指结构影响整合酶活性。本文总结了针对HIV Gag-Pol蛋白的抑制剂及其作用机制,并对已批准上市成药的用法用量进行综述,为今后临床联合用药和针对HIV Gag-pol蛋白的新型抑制剂开发提供参考。Gag-Pol protein is one of the important structural proteins of human immunodeficiency virus(HIV),comprising the basic scaffold proteins and functional enzymes required during the lifecycle of HIV.Currently,the inhibitors targeting different functional domains on Gag-Pol include capsid(CA)inhibitors,protease inhibitors,reverse transcriptase inhibitors,and integrase inhibitors.The CA inhibitors inhibit the maturation of CA or disrupt the assembly of CA,so as to affect the replication of HIV.The primary mechanism of protease inhibitors is to inhibit the protease from cleaving at the cleavage site CA-spacer peptide 1(SP1).The reverse transcriptase inhibitors block the reverse transcription process of HIV by mimicking the reverse transcription substrates.The integrase inhibitors impact the activity of integrase by targeting the zinc-finger structure at the active center of integrase.This article summarizes the inhibitors targeting HIV Gag-Pol protein and their mechanisms,and reviews the approved dosages and usages of approved patent drugs,so as to provide the references for the future clinical combination therapies and the development of new inhibitors targeting HIV Gag-Pol protein.

关 键 词：人类免疫缺陷型病毒 Gag-Pol蛋白 蛋白酶抑制剂 逆转录酶抑制剂 整合酶抑制剂 成熟抑制剂 

分 类 号：R512.91[医药卫生—内科学]