Model of the RNA Polymerase Complex of the SARS-CoV-2 Virus with Favipiravir

被引:3
|
作者
Polyakov, I. V. [1 ,2 ]
Grigorenko, B. L. [1 ,2 ]
Nemukhin, A. V. [1 ,2 ]
机构
[1] Russian Acad Sci, Emanuel Inst Biochem Phys, Moscow 119991, Russia
[2] Moscow MV Lomonosov State Univ, Moscow 119991, Russia
基金
俄罗斯基础研究基金会;
关键词
molecular dynamics; coronavirus; RNA polymerase; reaction mechanism; inhibition; favipiravir;
D O I
10.1134/S1990793121010255
中图分类号
O64 [物理化学(理论化学)、化学物理学]; O56 [分子物理学、原子物理学];
学科分类号
070203 ; 070304 ; 081704 ; 1406 ;
摘要
A model of a multidomain complex is constructed using molecular modeling methods to explain the mechanism of the inhibitory effect of favipiravir on RNA-dependent RNA polymerase (RdRp) of the SARS-CoV-2 coronavirus. As the initial atomic coordinates, we use cryoelectron microscopy data for the apo form of RdRp of the SARS-CoV-2 virus and data on the structure of RdRp of the hepatitis C virus. After appropriate substitutions, an RdRp complex containing RNA chains and a potential enzyme inhibitor, favipiravir in the form of ribosatriphosphate, are constructed. The structure of the complex in aqueous shells, which includes more than 100 000 atoms, is optimized by molecular dynamics methods. Analysis of the active site with the incorporated favipiravir molecule makes it possible to explain the chemical reaction of the enzyme with the inhibitor.
引用
收藏
页码:103 / 107
页数:5
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