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TitleThe binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses.
Journal, issue, pagesVirol Sin, Year 2024
Publish dateJun 10, 2024
AuthorsJunsen Chen / Junqing Sun / Zepeng Xu / Linjie Li / Xinrui Kang / Chunliang Luo / Qi Wang / Xueyang Guo / Yan Li / Kefang Liu / Ying Wu /
PubMed AbstractFoxes 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 ...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.
External linksVirol Sin / PubMed:38866203
MethodsEM (single particle)
Resolution2.96 - 3.47 Å
Structure data

EMDB-38784, PDB-8xyz:
The structure of fox ACE2 and PT RBD complex
Method: EM (single particle) / Resolution: 2.96 Å

EMDB-38792, PDB-8xzb:
The structure of fox ACE2 and SARS-CoV RBD complex
Method: EM (single particle) / Resolution: 3.12 Å

EMDB-38793, PDB-8xzd:
The structure of fox ACE2 and Omicron BF.7 RBD complex
Method: EM (single particle) / Resolution: 3.47 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • severe acute respiratory syndrome coronavirus 2
  • vulpes vulpes (red fox)
  • severe acute respiratory syndrome-related coronavirus
KeywordsVIRAL PROTEIN / fox ACE2/PT RBD / fox ACE2 SARS-CoV RBD / fox ACE2 / Omicron BF.7

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