Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure

PeerJ
G. B. ChandGajendra Kumar Azad

Abstract

The rapid development of the SARS-CoV-2 mediated COVID-19 pandemic has been the cause of significant health concern, highlighting the immediate need for effective antivirals. SARS-CoV-2 is an RNA virus that has an inherently high mutation rate. These mutations drive viral evolution and genome variability, thereby facilitating viruses to have rapid antigenic shifting to evade host immunity and to develop drug resistance. Viral RNA-dependent RNA polymerases (RdRp) perform viral genome duplication and RNA synthesis. Therefore, we compared the available RdRp sequences of SARS-CoV-2 from Indian isolates and the 'Wuhan wet sea food market virus' sequence to identify, if any, variation between them. Our data revealed the occurrence of seven mutations in Indian isolates of SARS-CoV-2. The secondary structure prediction analysis of these seven mutations shows that three of them cause alteration in the structure of RdRp. Furthermore, we did protein modelling studies to show that these mutations can potentially alter the stability of the RdRp protein. Therefore, we propose that RdRp mutations in Indian SARS-CoV-2 isolates might have functional consequences that can interfere with RdRp targeting pharmacological agents.

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Citations

Nov 19, 2020·Transboundary and Emerging Diseases·Fangfeng YuanLeyi Wang
Jan 22, 2021·Expert Opinion on Therapeutic Patents·Ilaria VicentiFrancesco Saladini
Feb 3, 2021·Biochemistry and Biophysics Reports·Gajendra Kumar Azad, Parimal Kumar Khan
Jan 27, 2021·JMIR Bioinformatics and Biotechnology·Anindita BanerjeeMamta Chawla-Sarkar
Feb 4, 2021·Biology·Santiago Vilar, Daniel G Isom
Feb 13, 2021·Pathogens·Alejandro Flores-AlanisRosario Morales-Espinosa
Jan 13, 2021·Journal of Medical Virology·Shamlan M S ReshamwalaSantosh B Noronha
Mar 23, 2021·ACS Omega·Muhammad Tahir KhanDong Qing Wei
May 8, 2021·Methods : a Companion to Methods in Enzymology·Ankur GuptaShailendra K Saxena
Jun 21, 2021·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·L Ponoop Prasad PatroThenmalarchelvi Rathinavelan
Aug 26, 2021·Communications Biology·Florian A JochheimPatrick Cramer

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Methods Mentioned

BETA
X-ray

Software Mentioned

CFSSP
Clustal Omega
DynaMut

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