The binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses

Junsen Chen; Junqing Sun; Zepeng Xu; Linjie Li; Xinrui Kang; Chunliang Luo; Qi Wang; Xueyang Guo; Yan Li; Kefang Liu; Ying Wu

doi:10.1016/j.virs.2024.06.004

August 2024

Citation: Junsen Chen, Junqing Sun, Zepeng Xu, Linjie Li, Xinrui Kang, Chunliang Luo, Qi Wang, Xueyang Guo, Yan Li, Kefang Liu, Ying Wu. The binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses .VIROLOGICA SINICA, 2024, 39(4) : 609-618. http://dx.doi.org/10.1016/j.virs.2024.06.004

The binding and structural basis of fox ACE2 to RBDs from different sarbecoviruses

Junsen Chen ^a ,
Junqing Sun ^b,c ,
Zepeng Xu ^b,d ,
Linjie Li ^b ,
Xinrui Kang ^b ,
Chunliang Luo ^b ,
Qi Wang ^a ,
Xueyang Guo ^a ,
Yan Li ^b ,
Kefang Liu ^{c
,,} ,
Ying Wu ^{a
,,}

cstr: 32224.14.j.virs.2024.06.004

a. State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China;
b. CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China;
c. Beijing Life Science Academy, Beijing, 102209, China;
d. Faculty of Health Sciences, University of Macau, Macau, SAR, 999078, China

Corresponding author: Kefang Liu, liukf@im.ac.cn
Ying Wu, yingwu@whu.edu.cn
Received Date: 19 March 2024
Accepted Date: 06 June 2024
Available online: 10 June 2024

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.
- Sarbecoviruses
- , SARS-CoV
- , SARS-CoV-2
- , Fox ACE2
- , Omicron
- , Cryo-EM structure

Electronic Supplementary Material

10.1016j.virs.2024.06.004-ESM.docx
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