Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31276-6
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Funding
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDB29010202]
- National Key Research and Development Program of China [2021YFC0863300]
- National Natural Science Foundation [32100752]
- Young Elite Scientists Sponsorship Program by CAST [2021QNRC001]
- China Post-doctoral Science Foundation [2021M700161]
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This study reveals the binding mechanism between equine ACE2 and SARS-CoV-2 and related coronaviruses, highlighting the importance of continuous surveillance on these viruses and their potential spillover events. Horses are identified as potential targets for SARS-CoV-2.
This study documents equine ACE2 (eqACE2) binding to the RBDs of SARS-CoV-2 and related CoVs, revealing a mechanism of eqACE2 binding with RaTG13-RBD, SARS-CoV-2 prototype-RBD and Omicron BA.1-RBD. The origin and host range of SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), are important scientific questions as they might provide insight into understanding of the potential future spillover to infect humans. Here, we tested the binding between equine angiotensin converting enzyme 2 (eqACE2) and the receptor binding domains (RBDs) of SARS-CoV, SARS-CoV-2 prototype (PT) and variant of concerns (VOCs), as well as their close relatives bat-origin coronavirus (CoV) RaTG13 and pangolin-origin CoVs GX/P2V/2017 and GD/1/2019. We also determined the crystal structures of eqACE2/RaTG13-RBD, eqACE2/SARS-CoV-2 PT-RBD and eqACE2/Omicron BA.1-RBD. We identified S494 of SARS-COV-2 PT-RBD as an important residue in the eqACE2/SARS-COV-2 PT-RBD interaction and found that N501Y, the commonly recognized enhancing mutation, attenuated the binding affinity with eqACE2. Our work demonstrates that horses are potential targets for SARS-CoV-2 and highlights the importance of continuous surveillance on SARS-CoV-2 and related CoVs to prevent spillover events.
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