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

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。

Abstract

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

Key words

Human immunodeficiency virus / Gag-Pol protein / Protease inhibitor / Reverse transcriptase inhibitor / Integrase inhibitor / Maturation inhibitor

Author summay

黄国锋（1999-），男，吉林省吉林市人，在读硕士研究生，主要从事分子生物学方面的研究。