tetano
Editor, Senior Moderator
Structure
. 2022 Jul 31;S0969-2126(22)00274-X.
doi: 10.1016/j.str.2022.07.005. Online ahead of print.
Structural insights into the binding of SARS-CoV-2, SARS-CoV, and hCoV-NL63 spike receptor-binding domain to horse ACE2
Jun Lan[SUP] 1 [/SUP], Peng Chen[SUP] 2 [/SUP], Weiming Liu[SUP] 3 [/SUP], Wenlin Ren[SUP] 4 [/SUP], Linqi Zhang[SUP] 2 [/SUP], Qiang Ding[SUP] 4 [/SUP], Qi Zhang[SUP] 5 [/SUP], Xinquan Wang[SUP] 6 [/SUP], Jiwan Ge[SUP] 7 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and human coronavirus (hCoV)-NL63 utilize ACE2 as the functional receptor for cell entry, which leads to zoonotic infection. Horses (Equus caballus) attracted our attention because the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 and SARS-CoV-2-related coronaviruses bind equine ACE2 (eACE2) with high affinity. Here we show that eACE2 binds the RBDs of these three coronaviruses and also SARS-CoV-2 variants but with lower affinities compared with human ACE2 (hACE2). Structural analysis and mutation assays indicated that eACE2-H41 accounts for the lower binding affinity of eACE2 to the RBDs of SARS-CoV-2 variants (Alpha, Beta, and Gamma), SARS-CoV, and hCoV-NL63. Pseudovirus infection assays showed that the SARS-CoV-2 Delta strain (B.1.617.2) displayed a significantly increased infection efficiency in eACE2-expressing HeLa cells. Our results reveal the molecular basis of eACE2 binding to the RBDs of SARS-CoV, SARS-CoV-2, and hCoV-NL63, which provides insights into the potential animal transmission of these ACE2-dependent coronaviruses.
Keywords: ACE2; SARS-CoV; SARS-CoV-2; complex structure; hCoV-NL63; horse; pseudovirus infection; receptor binding domain.
. 2022 Jul 31;S0969-2126(22)00274-X.
doi: 10.1016/j.str.2022.07.005. Online ahead of print.
Structural insights into the binding of SARS-CoV-2, SARS-CoV, and hCoV-NL63 spike receptor-binding domain to horse ACE2
Jun Lan[SUP] 1 [/SUP], Peng Chen[SUP] 2 [/SUP], Weiming Liu[SUP] 3 [/SUP], Wenlin Ren[SUP] 4 [/SUP], Linqi Zhang[SUP] 2 [/SUP], Qiang Ding[SUP] 4 [/SUP], Qi Zhang[SUP] 5 [/SUP], Xinquan Wang[SUP] 6 [/SUP], Jiwan Ge[SUP] 7 [/SUP]
Affiliations
- PMID: 35917815
- DOI: 10.1016/j.str.2022.07.005
Abstract
Severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and human coronavirus (hCoV)-NL63 utilize ACE2 as the functional receptor for cell entry, which leads to zoonotic infection. Horses (Equus caballus) attracted our attention because the spike protein receptor-binding domains (RBDs) of SARS-CoV-2 and SARS-CoV-2-related coronaviruses bind equine ACE2 (eACE2) with high affinity. Here we show that eACE2 binds the RBDs of these three coronaviruses and also SARS-CoV-2 variants but with lower affinities compared with human ACE2 (hACE2). Structural analysis and mutation assays indicated that eACE2-H41 accounts for the lower binding affinity of eACE2 to the RBDs of SARS-CoV-2 variants (Alpha, Beta, and Gamma), SARS-CoV, and hCoV-NL63. Pseudovirus infection assays showed that the SARS-CoV-2 Delta strain (B.1.617.2) displayed a significantly increased infection efficiency in eACE2-expressing HeLa cells. Our results reveal the molecular basis of eACE2 binding to the RBDs of SARS-CoV, SARS-CoV-2, and hCoV-NL63, which provides insights into the potential animal transmission of these ACE2-dependent coronaviruses.
Keywords: ACE2; SARS-CoV; SARS-CoV-2; complex structure; hCoV-NL63; horse; pseudovirus infection; receptor binding domain.