Cross-species recognition of bat coronavirus RsYN04 and cross-reaction of SARS-CoV-2 antibodies against the virus

Runchu Zhao; Sheng Niu; Pu Han; Yue Gao; Dezhi Liu; Chunliang Luo; Honghui Liu; Bo Liu; Yanli Xu; Jianxun Qi; Zhihai Chen; Weifeng Shi; Lili Wu; George F. Gao; Qihui Wang

doi:10.24272/j.issn.2095-8137.2023.187

Volume 44 Issue 6

Nov. 2023

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Article Navigation > Zoological Research > 2023 > 44(6): 1015-1025

Runchu Zhao, Sheng Niu, Pu Han, Yue Gao, Dezhi Liu, Chunliang Luo, Honghui Liu, Bo Liu, Yanli Xu, Jianxun Qi, Zhihai Chen, Weifeng Shi, Lili Wu, George F. Gao, Qihui Wang. Cross-species recognition of bat coronavirus RsYN04 and cross-reaction of SARS-CoV-2 antibodies against the virus. Zoological Research, 2023, 44(6): 1015-1025. doi: 10.24272/j.issn.2095-8137.2023.187

Citation:

Runchu Zhao, Sheng Niu, Pu Han, Yue Gao, Dezhi Liu, Chunliang Luo, Honghui Liu, Bo Liu, Yanli Xu, Jianxun Qi, Zhihai Chen, Weifeng Shi, Lili Wu, George F. Gao, Qihui Wang. Cross-species recognition of bat coronavirus RsYN04 and cross-reaction of SARS-CoV-2 antibodies against the virus. Zoological Research, 2023, 44(6): 1015-1025. doi: 10.24272/j.issn.2095-8137.2023.187

Citation:

Runchu Zhao, Sheng Niu, Pu Han, Yue Gao, Dezhi Liu, Chunliang Luo, Honghui Liu, Bo Liu, Yanli Xu, Jianxun Qi, Zhihai Chen, Weifeng Shi, Lili Wu, George F. Gao, Qihui Wang. Cross-species recognition of bat coronavirus RsYN04 and cross-reaction of SARS-CoV-2 antibodies against the virus. Zoological Research, 2023, 44(6): 1015-1025. doi: 10.24272/j.issn.2095-8137.2023.187

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Cross-species recognition of bat coronavirus RsYN04 and cross-reaction of SARS-CoV-2 antibodies against the virus

doi: 10.24272/j.issn.2095-8137.2023.187

Runchu Zhao^{1, 2, #},
Sheng Niu^{3, #},
Pu Han^{2, #},
Yue Gao^{2, 4},
Dezhi Liu^{1, 2},
Chunliang Luo^{2, 3},
Honghui Liu²,
Bo Liu^{2, 3},
Yanli Xu⁵,
Jianxun Qi²,
Zhihai Chen⁵,
Weifeng Shi⁶,
Lili Wu^{2
,
,},
George F. Gao^{2, 7},
Qihui Wang^{1, 2, 7
,
,}

1.
Institute of Physical Science and Information, Anhui University, Hefei, Anhui 230039, China
2.
CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
3.
College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi 030801, China
4.
School of Life Sciences, Hebei University, Baoding, Hebei 071002, China
5.
Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
6.
Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong 271000, China
7.
University of Chinese Academy of Sciences, Beijing 100049, China

The atomic coordinates for the RsYN04 RBD-S43 complex crystal structure were deposited in the Protein Data Bank (www.rcsb.org) (PDB ID code 8J5J).
Supplementary data to this article can be found online.
Q.W., G.F.G., H.L., B.L., and L.W. are listed as coinventors of the patent for the antibody S43. G.F.G. is the holder of the patent intellectual property for the ZF2001^® vaccine.
G.F.G. and Q.W. initiated and coordinated the project and designed the experiments. R.Z., Y.G., and D.L. performed the SPR and FACS analyses with help from L.W. and C.L. R.Z. and S.N. prepared the RsYN04 RBD-S43 crystals with help from H.L. and B.L. P.H. and J.Q. solved the structure. Z.C. and Y.X. provided the serum samples. W.S. provided the ACE2 sequence of R. stheno. R.Z., S.N., L.W., G.F.G., and Q.W. analyzed the data and wrote the manuscript. All authors read and approved the final version of the manuscript.
#Authors contributed equally to this work

Funds: This work was supported by the National Key R&D Program of China (2022YFC2303403) and National Natural Science Foundation of China (82225021). Q.W. was supported by the Chinese Academy of Sciences (YSBR-010 and Y2022037)

More Information

Corresponding author: E-mail: wulili@im.ac.cn; wangqihui@im.ac.cn
Received Date: 2023-08-24
Accepted Date: 2023-08-25

Published Online: 2023-09-13

Publish Date: 2023-11-18

Abstract

Abstract

Following the outbreak of coronavirus disease 2019 (COVID-19), several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related coronaviruses have been discovered. Previous research has identified a novel lineage of SARS-CoV-2-related CoVs in bats, including RsYN04, which recognizes human angiotensin-converting enzyme 2 (ACE2) and thus poses a potential threat to humans. Here, we screened the binding of the RsYN04 receptor-binding domain (RBD) to ACE2 orthologs from 52 animal species and found that the virus showed a narrower ACE2-binding spectrum than SARS-CoV-2. However, the presence of the T484W mutation in the RsYN04 RBD broadened its range. We also evaluated 44 SARS-CoV-2 antibodies targeting seven epitope communities in the SARS-CoV-2 RBD, together with serum obtained from COVID-19 convalescents and vaccinees, to determine their cross-reaction against RsYN04. Results showed that no antibodies, except for the RBD-6 and RBD-7 classes, bound to the RsYN04 RBD, indicating substantial immune differences from SARS-CoV-2. Furthermore, the structure of the RsYN04 RBD in complex with cross-reactive antibody S43 in RBD-7 revealed a potently broad epitope for the development of therapeutics and vaccines. Our findings suggest RsYN04 and other viruses belonging to the same clade have the potential to infect several species, including humans, highlighting the necessity for viral surveillance and development of broad anti-coronavirus countermeasures.
- SARS-CoV-2-related coronavirus,
- RsYN04,
- ACE2,
- Antibody,
- Structure

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References(44)

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