Molecular Level Dissection of Critical Spike Mutations in SARS‐CoV‐2 Variants of Concern (VOCs): A Simplified Review

Joshi, Nilesh; Tyagi, Adish; Nigam, Sandeep

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.