tetano
Editor, Senior Moderator
PLoS Comput Biol
. 2022 Jul 11;18(7):e1009834.
doi: 10.1371/journal.pcbi.1009834. Online ahead of print.
Analysis of the docking property of host variants of hACE2 for SARS-CoV-2 in a large cohort
Hyojung Paik[SUP] 1 2 [/SUP], Jimin Kim[SUP] 1 [/SUP], Sangjae Seo[SUP] 1 [/SUP]
Affiliations
Abstract
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.
. 2022 Jul 11;18(7):e1009834.
doi: 10.1371/journal.pcbi.1009834. Online ahead of print.
Analysis of the docking property of host variants of hACE2 for SARS-CoV-2 in a large cohort
Hyojung Paik[SUP] 1 2 [/SUP], Jimin Kim[SUP] 1 [/SUP], Sangjae Seo[SUP] 1 [/SUP]
Affiliations
- PMID: 35816517
- DOI: 10.1371/journal.pcbi.1009834
Abstract
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.