Most frequently harboured missense variants of hACE2 across different populations exhibit varying patterns of binding interaction with spike glycoproteins of emerging SARS-CoV-2 of different lineages

• Published in: Computers in biology and medicine 2022-09, Vol.148, p.105903-105903, Article 105903
• Main Authors: Tahsin, Anika, Ahmed, Rubaiat, Bhattacharjee, Piyash, Adiba, Maisha, Al Saba, Abdullah, Yasmin, Tahirah, Chakraborty, Sajib, Hasan, A.K.M. Mahbub, Nabi, A.H.M. Nurun
• Format: Article
• Language: English
• Subjects: ACE2; Amino acids; Angiotensin; Angiotensin-Converting Enzyme 2; Binding; Coronaviruses; COVID-19; Disease transmission; Dynamic stability; Enzymes; Genetic factors; Genomes; Glycoproteins; hACE2; Humans; Infectivity; Missense variants; MM/GBSA; Molecular docking; Molecular Docking Simulation; Molecular dynamics; Mutation; Peptidyl-Dipeptidase A; Physiology; Polymorphism; Population; Populations; Protein Binding; Proteins; Receptors; Receptors, Virus; RNA polymerase; SARS-CoV-2; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Simulation; Spike glycoprotein; Spike Glycoprotein, Coronavirus; Stability analysis; Viral diseases; Virulence; Viruses
• ISSN: 0010-4825; 1879-0534
• DOI: 10.1016/j.compbiomed.2022.105903

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. •The binding of SARS-CoV-2 spike RBD differs markedly, based on hACE2 polymorphisms.•Insights into differential spread of various SARS-CoV-2 variants across populations.•Omicron BA.2 shows most stable binding, favouring greater spread across the world.•Lineage defining mutations may stabilise or destabilise the spike protein residues.