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.
ABSTRACT
Abstract The COVID-19 pandemic caused by SARS-CoV-2 is a global health emergency. Investigation covering various aspects of diagnosis, treatment, and vaccine development for COVID-19 are being attempted globally. Common goal of reducing loss of life requires accelerated and integrated effort from researchers of different fields i.?e. chemistry, biology, clinical/medical science etc. Integrated yet timely effort requires the understanding of interdisciplinary key concepts as well as knowledge of major challenges, present status and strategies. Hence, in this article, we present an overview of baseline/key facts of SARS-CoV-2 mingled with current status and strategies in a simple, straight forward and coherent manner. In particular, the review attempts to integrate and arrange the key facts at the interface of chemistry and biology. Overview of epidemiology of SARS-CoV-2 virus infection, structural characteristics of virus, detection methods and therapeutic agents based on antibodies, therapeutic agents based on traditional drug molecule, drug development based on specific catalytic enzyme inhibitors, vaccine design approaches have been provided. Since enzyme site and catalytic action is the key for biological process, they have been lucidly explained at molecular level. It is believed that accredited information amalgamated in this report will provide a strong rational and lucid groundwork for the coherent interdisciplinary research to countermeasure covid-19 crisis.