新型冠状病毒主蛋白酶天然产物抑制剂的筛选  

Screening of natural product inhibitors targeting SARS-CoV-2 main protease

作　　者：师云凡 鞠壮 丁显平[1,2] SHI Yun-Fan;JU Zhuang;DING Xian-Ping(College of Life Sciences,Sichuan University,Chengdu 610065,China;Joint Key Lab of Sichuan&Chongqing,Bioresource Res&Utilizat,Nanchuan 408400,China)

机构地区：[1]四川大学生命科学学院,成都610065 [2]特色生物资源研究与利用川渝共建重点实验室,南川408400

出　　处：《四川大学学报（自然科学版）》2023年第4期152-158,共7页Journal of Sichuan University(Natural Science Edition)

基　　金：四川省科技厅项目(2020JDS0039)。

摘　　要：为寻找新型冠状病毒主蛋白酶天然产物抑制剂,本文以SARS-CoV-2主蛋白酶为研究对象,通过计算机辅助药物筛选方法初步筛选出16个潜在抑制剂并进行体外酶活测试.其中,野黄岑素对SARS-CoV-2主蛋白酶的IC_(50)为(10.79±2.116)μmol/L,没食子儿茶素没食子酸酯抑制SARS-CoV-2主蛋白酶的IC_(50)为(2.104±0.346)μmol/L.最后,将两种天然产物与主蛋白酶进行分子动力学模拟发现没食子儿茶素没食子酸酯和野黄岑素与新型冠状病毒主蛋白酶结合时的复合物RMSD都在0.22附近,说明两个天然产物与新型冠状病毒主蛋白酶结合较为稳定,可以作为新型冠状病毒主蛋白酶的抑制剂或先导化合物.To screen natural product inhibitors targeting the SARS-CoV-2 main protease,this paper takes the main peoteases of SARS-Cov-2 as the research object,and 16 potential inhibitors were preliminarily screened by computer-aided drug screening method and tested for enzyme activity in vitro.Among them,the IC_(50)of scutellarin against SARS-CoV-2 main protease was(10.79±2.116)μmol/L.The IC_(50)of(-)-Gallocatechin gallate against SARS-CoV-2 main protease was(2.104±0.346)μmol/L.Finally,molecular dynamics simulations were performed on the two natural products and Mpro.It was found that the RMSD of the complexes of(-)-Gallocatechin gallate and Scutellarein with Mpro was around 0.22,indicating that the two natural products were stable in binding with Mpro and could be used as inhibitors or lead compounds of Mpro in SARS-CoV-2.

关 键 词：新型冠状病毒主蛋白酶 基于结构的虚拟筛选 没食子儿茶素没食子酸酯 野黄岺素 分子动力学模拟 

分 类 号：Q55[生物学—生物化学] R914[医药卫生—药物化学]