Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight

The recent emergence of novel SARS-CoV-2 variants has threatened the efforts to contain the COVID-19 pandemic. The emergence of these “variants of concern” has increased immune escape and has supplanted the ancestral strains. The novel variants harbored by the B.1.617 lineage (kappa and delta) carry...

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Autores principales:	Mohd Imran Khan, Mohammad Hassan Baig, Tanmoy Mondal, Mohammed Alorabi, Tanuj Sharma, Jae-June Dong, Jae Yong Cho
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	SARS-CoV-2 COVID-19 variant molecular dynamics double mutant delta variant Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/879cd0823ef04ae89f20e482c6a154ba
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spelling	oai:doaj.org-article:879cd0823ef04ae89f20e482c6a154ba2021-11-25T19:14:17ZImpact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight10.3390/v131122951999-4915https://doaj.org/article/879cd0823ef04ae89f20e482c6a154ba2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2295https://doaj.org/toc/1999-4915The recent emergence of novel SARS-CoV-2 variants has threatened the efforts to contain the COVID-19 pandemic. The emergence of these “variants of concern” has increased immune escape and has supplanted the ancestral strains. The novel variants harbored by the B.1.617 lineage (kappa and delta) carry mutations within the receptor-binding domain of spike (S) protein (L452R + E484Q and L452R + T478K), the region binding to the host receptor. The double mutations carried by these novel variants are primarily responsible for an upsurge number of COVID-19 cases in India. In this study, we thoroughly investigated the impact of these double mutations on the binding capability to the human host receptor. We performed several structural analyses and found that the studied double mutations increase the binding affinity of the spike protein to the human host receptor (ACE2). Furthermore, our study showed that these double mutants might be a dominant contributor enhancing the receptor-binding affinity of SARS-CoV-2 and consequently making it more stable. We also investigated the impact of these mutations on the binding affinity of two monoclonal antibodies (Abs) (2-15 and LY-CoV555) and found that the presence of the double mutations also hinders its binding with the studied Abs. The principal component analysis, free energy landscape, intermolecular interaction, and other investigations provided a deeper structural insight to better understand the molecular mechanism responsible for increased viral transmissibility of these variants.Mohd Imran KhanMohammad Hassan BaigTanmoy MondalMohammed AlorabiTanuj SharmaJae-June DongJae Yong ChoMDPI AGarticleSARS-CoV-2COVID-19variantmolecular dynamicsdouble mutantdelta variantMicrobiologyQR1-502ENViruses, Vol 13, Iss 2295, p 2295 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 COVID-19 variant molecular dynamics double mutant delta variant Microbiology QR1-502
spellingShingle	SARS-CoV-2 COVID-19 variant molecular dynamics double mutant delta variant Microbiology QR1-502 Mohd Imran Khan Mohammad Hassan Baig Tanmoy Mondal Mohammed Alorabi Tanuj Sharma Jae-June Dong Jae Yong Cho Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight
description	The recent emergence of novel SARS-CoV-2 variants has threatened the efforts to contain the COVID-19 pandemic. The emergence of these “variants of concern” has increased immune escape and has supplanted the ancestral strains. The novel variants harbored by the B.1.617 lineage (kappa and delta) carry mutations within the receptor-binding domain of spike (S) protein (L452R + E484Q and L452R + T478K), the region binding to the host receptor. The double mutations carried by these novel variants are primarily responsible for an upsurge number of COVID-19 cases in India. In this study, we thoroughly investigated the impact of these double mutations on the binding capability to the human host receptor. We performed several structural analyses and found that the studied double mutations increase the binding affinity of the spike protein to the human host receptor (ACE2). Furthermore, our study showed that these double mutants might be a dominant contributor enhancing the receptor-binding affinity of SARS-CoV-2 and consequently making it more stable. We also investigated the impact of these mutations on the binding affinity of two monoclonal antibodies (Abs) (2-15 and LY-CoV555) and found that the presence of the double mutations also hinders its binding with the studied Abs. The principal component analysis, free energy landscape, intermolecular interaction, and other investigations provided a deeper structural insight to better understand the molecular mechanism responsible for increased viral transmissibility of these variants.
format	article
author	Mohd Imran Khan Mohammad Hassan Baig Tanmoy Mondal Mohammed Alorabi Tanuj Sharma Jae-June Dong Jae Yong Cho
author_facet	Mohd Imran Khan Mohammad Hassan Baig Tanmoy Mondal Mohammed Alorabi Tanuj Sharma Jae-June Dong Jae Yong Cho
author_sort	Mohd Imran Khan
title	Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight
title_short	Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight
title_full	Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight
title_fullStr	Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight
title_full_unstemmed	Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight
title_sort	impact of the double mutants on spike protein of sars-cov-2 b.1.617 lineage on the human ace2 receptor binding: a structural insight
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/879cd0823ef04ae89f20e482c6a154ba
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Impact of the Double Mutants on Spike Protein of SARS-CoV-2 B.1.617 Lineage on the Human ACE2 Receptor Binding: A Structural Insight

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