Analysis of the docking property of host variants of hACE2 for SARS-CoV-2 in a large cohort

• Published in: PLoS computational biology Vol. 18; no. 7; p. e1009834
• Main Authors: Paik, Hyojung, Kim, Jimin, Seo, Sangjae
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.07.2022; Public Library of Science (PLoS)
• Subjects: ACE2; Amino acids; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - genetics; Biobanks; Biology and life sciences; Coronaviruses; COVID-19; COVID-19 - epidemiology; COVID-19 - genetics; COVID-19 vaccines; Disease transmission; Free energy; Genetic diversity; Global health; Health risks; Host-virus relationships; Humans; Infections; Medicine and health sciences; Microbiological research; Middle East respiratory syndrome; Molecular dynamics; Molecular interactions; Mutagenesis; Mutation; Pandemics; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Physical Sciences; Population; Protein Binding; Proteins; Public health; SARS-CoV-2 - genetics; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike protein; Trends; Viral diseases; Viral infections; South Korea; United Kingdom > UK
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1009834

The recent novel coronavirus disease (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is threatening global health. However, an understanding of the interaction of SARS-CoV-2 with human cells, including the physical docking property influenced by the host's genetic diversity, is still lacking. Here, based on germline variants in the UK Biobank covering 502,543 individuals, we revealed the molecular interactions between human angiotensin-converting enzyme 2 (hACE2), which is the representative receptor for SARS-CoV-2 entry, and COVID-19 infection. We identified six nonsense and missense variants of hACE2 from 2585 subjects in the UK Biobank covering 500000 individuals. Using our molecular dynamics simulations, three hACE2 variants from 2585 individuals we selected showed higher levels of binding free energy for docking in the range of 1.44-3.69 kcal/mol. Although there are diverse contributors to SARS-CoV-2 infections, including the mobility of individuals, we analyzed the diagnosis records of individuals with these three variants of hACE2. Our molecular dynamics simulations combined with population-based genomic data provided an atomistic understanding of the interaction between hACE2 and the spike protein of SARS-CoV-2.