tetano
Editor, Senior Moderator
J Gen Virol
. 2020 Jun 15.
doi: 10.1099/jgv.0.001452. Online ahead of print.
Molecular Simulation of SARS-CoV-2 Spike Protein Binding to Pangolin ACE2 or Human ACE2 Natural Variants Reveals Altered Susceptibility to Infection
Jingfang Wang[SUP] 1 [/SUP], Xintian Xu[SUP] 2 1 [/SUP], Xinbo Zhou[SUP] 3 [/SUP], Ping Chen[SUP] 4 5 [/SUP], Huiying Liang[SUP] 4 [/SUP], Xuan Li[SUP] 5 [/SUP], Wu Zhong[SUP] 3 [/SUP], Pei Hao[SUP] 2 4 1 [/SUP]
Affiliations
Abstract
We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol[SUP]-1[/SUP]). Human ACE2 is among the most polymorphous genes, for which we identified 317 missense single-nucleotide variations (SNVs) from the dbSNP database. Three SNVs, E329G (rs143936283), M82I (rs267606406) and K26R (rs4646116), had a significant reduction in binding free energy, which indicated higher binding affinity than wild-type ACE2 and greater susceptibility to SARS-CoV-2 infection for people with them. Three other SNVs, D355N (rs961360700), E37K (rs146676783) and I21T (rs1244687367), had a significant increase in binding free energy, which indicated lower binding affinity and reduced susceptibility to SARS-CoV-2 infection.
Keywords: ACE2 variants; SARS-CoV-2; coronavirus; molecular dynamic simulation; pangolin; susceptibility.
. 2020 Jun 15.
doi: 10.1099/jgv.0.001452. Online ahead of print.
Molecular Simulation of SARS-CoV-2 Spike Protein Binding to Pangolin ACE2 or Human ACE2 Natural Variants Reveals Altered Susceptibility to Infection
Jingfang Wang[SUP] 1 [/SUP], Xintian Xu[SUP] 2 1 [/SUP], Xinbo Zhou[SUP] 3 [/SUP], Ping Chen[SUP] 4 5 [/SUP], Huiying Liang[SUP] 4 [/SUP], Xuan Li[SUP] 5 [/SUP], Wu Zhong[SUP] 3 [/SUP], Pei Hao[SUP] 2 4 1 [/SUP]
Affiliations
- PMID: 32538738
- DOI: 10.1099/jgv.0.001452
Abstract
We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol[SUP]-1[/SUP]). Human ACE2 is among the most polymorphous genes, for which we identified 317 missense single-nucleotide variations (SNVs) from the dbSNP database. Three SNVs, E329G (rs143936283), M82I (rs267606406) and K26R (rs4646116), had a significant reduction in binding free energy, which indicated higher binding affinity than wild-type ACE2 and greater susceptibility to SARS-CoV-2 infection for people with them. Three other SNVs, D355N (rs961360700), E37K (rs146676783) and I21T (rs1244687367), had a significant increase in binding free energy, which indicated lower binding affinity and reduced susceptibility to SARS-CoV-2 infection.
Keywords: ACE2 variants; SARS-CoV-2; coronavirus; molecular dynamic simulation; pangolin; susceptibility.