Molecular Level Dissection of Critical Spike Mutations in SARS‐CoV‐2 Variants of Concern (VOCs): A Simplified Review
Open Access
- 17 August 2021
- journal article
- review article
- Published by Wiley in ChemistrySelect
- Vol. 6 (31), 7981-7998
- https://doi.org/10.1002/slct.202102074
Abstract
SARS-CoV-2 virus during its spread in the last one and half year has picked up critical changes in its genetic code i.e. mutations, which have leads to deleterious epidemiological characteristics. Due to critical role of spike protein in cell entry and pathogenesis, mutations in spike regions have been reported to enhance transmissibility, disease severity, possible escape from vaccine-induced immune response and reduced diagnostic sensitivity/specificity. Considering the structure-function impact of mutations, understanding the molecular details of these key mutations of newly emerged variants/lineages is of urgent concern. In this review, we have explored the literature on key spike mutations harbored by alpha, beta, gamma and delta ‘variants of concern’ (VOCs) and discussed their molecular consequences in the context of resultant virus biology. Commonly all these VOCs i.e. B.1.1.7, B.1.351, P.1 and B.1.617.2 lineages have decisive mutation in Receptor Binding Motif (RBM) region and/or region around Furin cleavage site (FCS) of spike protein. In general, mutation induced disruption of intra-molecular interaction enhances molecular flexibility leading to exposure of spike protein surface in these lineages to make it accessible for inter-molecular interaction with hACE2. A disruption of spike antigen-antibody inter-molecular interactions in epitope region due to the chemical nature of substituting amino acid hampers the neutralization efficacy. Simplified surveillance of mutation induced changes and their consequences at molecular level can contribute in rationalizing mutation‘s impact on virus biology. It is believed that molecular level dissection of these key spike mutation will assist the future investigations for a more resilient outcome against severity of COVID-19.Keywords
This publication has 90 references indexed in Scilit:
- Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor bindingThe Lancet, 2020
- Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting WuhanEmerging Microbes & Infections, 2020
- Application of stochastic linear programming in managerial accountingInternational Journal of Accounting & Information Management, 2020
- Molecular epidemiology, evolution and phylogeny of SARS coronavirusInfection, Genetics and Evolution, 2019
- Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmissionScientific Reports, 2018
- Why are RNA virus mutation rates so damn high?PLoS Biology, 2018
- Mutations at protein-protein interfaces: Small changes over big surfaces have large impacts on human healthProgress in Biophysics and Molecular Biology, 2017
- Dipeptidyl Peptidase 4 Distribution in the Human Respiratory TractThe American Journal of Pathology, 2015
- Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome CoronavirusJournal of Virology, 2015
- SARS-CoV and emergent coronaviruses: viral determinants of interspecies transmissionCurrent Opinion in Virology, 2011