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

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 variab...

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Autores principales: Chand, Gyanendra Bahadur, Banerjee, Atanu, Azad, Gajendra Kumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337032/
https://www.ncbi.nlm.nih.gov/pubmed/32685291
http://dx.doi.org/10.7717/peerj.9492
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author Chand, Gyanendra Bahadur
Banerjee, Atanu
Azad, Gajendra Kumar
author_facet Chand, Gyanendra Bahadur
Banerjee, Atanu
Azad, Gajendra Kumar
author_sort Chand, Gyanendra Bahadur
collection PubMed
description 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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spelling pubmed-73370322020-07-17 Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure Chand, Gyanendra Bahadur Banerjee, Atanu Azad, Gajendra Kumar PeerJ Biochemistry 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. PeerJ Inc. 2020-07-03 /pmc/articles/PMC7337032/ /pubmed/32685291 http://dx.doi.org/10.7717/peerj.9492 Text en © 2020 Chand et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Biochemistry
Chand, Gyanendra Bahadur
Banerjee, Atanu
Azad, Gajendra Kumar
Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure
title Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure
title_full Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure
title_fullStr Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure
title_full_unstemmed Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure
title_short Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure
title_sort identification of novel mutations in rna-dependent rna polymerases of sars-cov-2 and their implications on its protein structure
topic Biochemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337032/
https://www.ncbi.nlm.nih.gov/pubmed/32685291
http://dx.doi.org/10.7717/peerj.9492
work_keys_str_mv AT chandgyanendrabahadur identificationofnovelmutationsinrnadependentrnapolymerasesofsarscov2andtheirimplicationsonitsproteinstructure
AT banerjeeatanu identificationofnovelmutationsinrnadependentrnapolymerasesofsarscov2andtheirimplicationsonitsproteinstructure
AT azadgajendrakumar identificationofnovelmutationsinrnadependentrnapolymerasesofsarscov2andtheirimplicationsonitsproteinstructure