Abstract
Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) is composed of four structural proteins and several accessory non-structural proteins. SARS-CoV-2’s most abundant structural protein, Membrane (M) protein, has a pivotal role both during viral infection cycle and host interferon antagonism. This is a highly conserved viral protein, thus an interesting and suitable target for drug discovery. In this paper, we explain the structural nature of M protein homodimer. To do so, we developed and applied a detailed and robust in silico workflow to predict M protein dimeric structure, membrane orientation, and interface characterization. Single Nucleotide Polymorphisms (SNPs) in M protein were retrieved from over 1.2 M SARS-CoV-2 genomes and proteins from the Global Initiative on Sharing All Influenza Data (GISAID) database, 91 of which were located at the predicted dimer interface. Among those, we identified SNPs in Variants of Concern (VOC) and Variants of Interest (VOI). Binding free energy differences were evaluated for dimer interfacial SNPs to infer mutant protein stabilities. A few high-prevalent mutated residues were found to be especially relevant in VOC and VOI. This realization may be a game-changer to structure-driven formulation of new therapeutics for SARS-CoV-2.
Highlights
COronaVIrus Disease 2019 (COVID-19) is currently a worldwide pandemic that was first reported in December 2019 in Wuhan, China, and, since led to more than446 M infected people and over 6.00 M deaths [1]
COVID-19 is caused by Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), which is a Coronaviridae family, positive single-stranded RiboNucleic Acid virus [2,3]
Since the beginning of this pandemic, SARS-CoV-2 has mutated over time, leading to the identification of several variants that, based on phylogeny [4], have been organized into clades named L, S, V, G, GH, GR, GV, GRY, and O [5,6]
Summary
COronaVIrus Disease 2019 (COVID-19) is currently a worldwide pandemic that was first reported in December 2019 in Wuhan, China, and, since led to more than446 M infected people and over 6.00 M deaths [1] (as of 7 March 2022). COronaVIrus Disease 2019 (COVID-19) is currently a worldwide pandemic that was first reported in December 2019 in Wuhan, China, and, since led to more than. COVID-19 is caused by Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), which is a Coronaviridae family, positive single-stranded RiboNucleic Acid (ssRNA) virus [2,3]. According to the World Health Organization (WHO), there are Variants Of Interest (VOI), variants that have been recognized as being able to acquire community transmission causing clusters and being further identified in several countries, or assessed as a VOI 4.0/). Variants Of Concern (VOC) are variants that, adding to the characterization as VOI, are linked to increased transmissibility or virulence, and/or a decrease in the effectiveness of treatment, prevention, and diagnosis approaches currently used.
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