新型冠状病毒RNA依赖性RNA聚合酶抑制剂研究进展  

Progress research on inhibitors of SARS-CoV-2 RNA dependent RNA Polymerase

作　　者：堵兴轶 胡泽涛 周欣梅 何新华 任旭红[1] DU Xingyi;HU Zetao;ZHOU Xinmei;HE Xinhua;REN Xuhong(School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China;Intelligent Biomedicine Research Center,Nanhu Laboratory,Jiaxing 314000,China)

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016 [2]南湖实验室数字生命和智能医学项目中心,浙江嘉兴314000

出　　处：《沈阳药科大学学报》2024年第4期500-517,536,共19页Journal of Shenyang Pharmaceutical University

基　　金：辽宁省教育厅基础研究项目(JYTM20231363);辽宁省科技厅化学原料药制药工艺过程安全评估平台资助项目(2023JH1/11400001)。

摘　　要：由严重急性呼吸综合征冠状病毒2型导致的新型冠状病毒感染席卷全球,寻找广谱抗病毒特效药一直是一项重大任务。RNA病毒的RNA依赖性RNA聚合酶是一类不同病毒间在结构和功能上高度保守的关键非结构蛋白,针对该聚合酶为靶点开发新的小分子抑制剂至关重要。本文作者从新型冠状病毒RNA依赖性RNA聚合酶的结构为出发点,详细阐述了该病毒RNA依赖性RNA聚合酶的作用机制以及不同种类抑制剂的特点。着重从药物化学的角度介绍了核苷类似物和非核苷类似物的作用特点和作用机制,综述了多种小分子聚合酶抑制剂化学结构与生物活性之间的关系。Objective The epidemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 has caused a global pandemic,so it is important to find broad-spectrum antiviral drugs.RNA-dependent RNA polymerase of RNA virus is a kind of non-structural protein which is highly conserved in structure and function among different viruses.It is important to develop new small molecular inhibitors targeting this polymerase.In this review,starting from the structure of SARS-CoV-2 RNA-dependent RNA polymerase,we expounded the mechanism of the viral RNA-dependent RNA polymerase and the characteristics of different kinds of inhibitors.The action characteristics and mechanism of nucleoside analogues and non-nucleoside analogues were introduced from the perspective of medicinal chemistry.We reviewed the relationship between the chemical structure and biological activity of many small molecular polymerase inhibitors.

关 键 词：RNA依赖性RNA聚合酶 抑制剂 核苷类似物 非核苷类似物 新型冠状病毒 

分 类 号：R914.2[医药卫生—药物化学]