Binding and structural basis of equine ACE2 to RBDs from SARS-CoV, SARS-CoV-2 and related coronaviruses

• Published in: Nature communications Vol. 13; no. 1; p. 3547
• Main Authors: Xu, Zepeng, Kang, Xinrui, Han, Pu, Du, Pei, Li, Linjie, Zheng, Anqi, Deng, Chuxia, Qi, Jianxun, Zhao, Xin, Wang, Qihui, Liu, Kefang, Gao, George Fu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.06.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 38/1; 38/22; 38/35; 38/44; 38/77; 631/326/421; 631/326/596/4130; 631/535/1266/1265; 82/103; 82/16; 82/29; 82/83; ACE2; Angiotensin; Angiotensin-Converting Enzyme 2; Animals; Binding; Coronaviruses; COVID-19; Crystal structure; Horses; Host range; Humanities and Social Sciences; multidisciplinary; Mutation; Peptidyl-dipeptidase A; Peptidyl-Dipeptidase A - metabolism; Protein Binding; Prototypes; SARS-CoV-2 - genetics; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - metabolism; Viral diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-31276-6

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. 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.