Abstract
Since the emergence of SARS-CoV-2 at Wuhan in the Hubei province of China in 2019, the virus has accumulated various mutations, giving rise to many variants. According to the combinations of mutations acquired, these variants are classified into lineages and greatly differ in infectivity and transmissibility. In 2021 alone, a variant of interest (VoI) Mu (B.1.621), as well as, variants of concern (VoC) Delta (B.1.617.2) and Omicron (BA.1, BA.2) and later in 2022, BA.4, BA.5, and BA.2.12.1 have emerged. Since then, the world has seen prominent surges in the rate of infection during short periods of time. However, not all populations have suffered equally, which suggests a possible role of host genetic factors. Here, we investigated the strength of binding of the spike glycoprotein receptor-binding domain (RBD) of the SARS-CoV-2 variants: Mu, Delta, Delta Plus (AY.1), Omicron sub-variants BA.1, BA.2, BA.4, BA.5, and BA.2.12.1 with the human angiotensin-converting enzyme 2 (hACE2) missense variants prevalent in major populations. In this purpose, molecular docking analysis, as well as, molecular dynamics simulation was performed of the above-mentioned SARS-CoV-2 RBD variants with the hACE2 containing the single amino acid substitutions prevalent in African (E37K), Latin American (F40L), non-Finnish European (D355 N), and South Asian (P84T) populations, in order to predict the effects of the lineage-defining mutations of the viral variants on receptor binding. The effects of these mutations on protein stability were also explored. The protein-protein docking and molecular dynamics simulation analyses have revealed variable strength of attachment and exhibited altered interactions in the case of different hACE2-RBD complexes. In vitro studies are warranted to confirm these findings which may enable early prediction regarding the risk of transmissibility of newly emerging variants across different populations in the future.
Keywords: COVID-19; MM/GBSA; Missense variants; Molecular docking; Molecular dynamics; SARS-CoV-2; hACE2.
【저자키워드】 COVID-19, SARS-CoV-2, molecular docking, molecular dynamics, hACE2., MM/GBSA, Missense variants, 【초록키워드】 Mutation, Genetic, mutations, variant, spike glycoprotein, variants of concern, Delta, B.1.617.2, risk, docking, omicron, virus, variants, Population, hACE2, Molecular dynamics simulation, China, Transmissibility, RBD, African, Wuhan, Lineage, Factors, protein stability, viral variant, predict, B.1.621, binding, Combination, Interaction, Receptor binding, AY.1, SARS-CoV-2 RBD, Complexes, domain, human Angiotensin-converting enzyme, molecular docking analysis, South Asian, missense variant, amino acid substitution, Host, Effect, populations, prevalent, investigated, was performed, exhibited, analysis, suffered, accumulated, Latin, non-Finnish European, rate of infection, the SARS-CoV-2, 【제목키워드】 spike glycoprotein, Population, hACE2, Lineage, missense variant, MOST, binding interaction,