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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

Authors
 Mohd Imran Khan  ;  Mohammad Hassan Baig  ;  Tanmoy Mondal  ;  Mohammed Alorabi  ;  Tanuj Sharma  ;  Jae-June Dong  ;  Jae Yong Cho 
Citation
 VIRUSES-BASEL, Vol.13(11) : 2295, 2021-11 
Journal Title
VIRUSES-BASEL
Issue Date
2021-11
MeSH
Angiotensin-Converting Enzyme 2 / chemistry* ; Angiotensin-Converting Enzyme 2 / immunology ; Antibodies, Monoclonal, Humanized / immunology ; Antibodies, Neutralizing / immunology ; Antibodies, Viral / immunology ; Binding Sites ; COVID-19 / immunology ; COVID-19 / transmission ; COVID-19 / virology* ; Humans ; India ; Molecular Dynamics Simulation* ; Mutation ; Protein Binding ; Protein Conformation ; SARS-CoV-2 / chemistry* ; SARS-CoV-2 / genetics ; SARS-CoV-2 / immunology ; SARS-CoV-2 / pathogenicity ; Spike Glycoprotein, Coronavirus / chemistry* ; Spike Glycoprotein, Coronavirus / genetics ; Spike Glycoprotein, Coronavirus / immunology
Keywords
COVID-19 ; SARS-CoV-2 ; delta variant ; double mutant ; kappa variant ; molecular dynamics ; variant
Abstract
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.
Files in This Item:
T202105492.pdf Download
DOI
10.3390/v13112295
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Family Medicine (가정의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Dong, Jae June(동재준) ORCID logo https://orcid.org/0000-0002-2420-2155
Cho, Jae Yong(조재용) ORCID logo https://orcid.org/0000-0002-0926-1819
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187313
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