The binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses.
Virol Sin
; 39(4): 609-618, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38866203
ABSTRACT
Foxes are susceptible to SARS-CoV-2 in laboratory settings, and there have also been reports of natural infections of both SARS-CoV and SARS-CoV-2 in foxes. In this study, we assessed the binding capacities of fox ACE2 to important sarbecoviruses, including SARS-CoV, SARS-CoV-2, and animal-origin SARS-CoV-2 related viruses. Our findings demonstrated that fox ACE2 exhibits broad binding capabilities to receptor-binding domains (RBDs) of sarbecoviruses. We further determined the cryo-EM structures of fox ACE2 complexed with RBDs of SARS-CoV, SARS-CoV-2 prototype (PT), and Omicron BF.7. Through structural analysis, we identified that the K417 mutation can weaken the ability of SARS-CoV-2 sub-variants to bind to fox ACE2, thereby reducing the susceptibility of foxes to SARS-CoV-2 sub-variants. In addition, the Y498 residue in the SARS-CoV RBD plays a crucial role in forming a vital cation-π interaction with K353 in the fox ACE2 receptor. This interaction is the primary determinant for the higher affinity of the SARS-CoV RBD compared to that of the SARS-CoV-2 PT RBD. These results indicate that foxes serve as potential hosts for numerous sarbecoviruses, highlighting the critical importance of surveillance efforts.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Binding
/
Foxes
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Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
Limits:
Animals
/
Humans
Language:
En
Journal:
Virol Sin
/
Virol. sin. (Online)
/
Virologica sinica (Online)
Journal subject:
VIROLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Países Bajos