Structural insights into the binding of SARS-CoV-2, SARS-CoV, and hCoV-NL63 spike receptor-binding domain to horse ACE2.
Structure
; 30(10): 1432-1442.e4, 2022 10 06.
Article
in English
| MEDLINE | ID: covidwho-1967156
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
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Coronavirus NL63, Human
/
COVID-19
Topics:
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Structure
Journal subject:
Molecular Biology
/
Biochemistry
/
Biotechnology
Year:
2022
Document Type:
Article
Affiliation country:
J.str.2022.07.005
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