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Author Notes:

Qihui Wang, wangqihui@im.ac.cn; George F. Gao, gaof@im.ac.cn; Jianxun Qi, jxqi@im.ac.cn

J.Q., G.F.G., and Q.W. initiated and designed the project. K.L. and X.P. purified the proteins and grew the crystals with help from Y.M., Y.Z., L.W., and C.S. X.P. and L.L. performed the SPR analysis with help from Y.J., S.N., and C.Q. K.L., X.P., and L.L. conducted the flow cytometry assay with help from A.Z., Q.C., and L.W. F.Y. and J.Q. collected the structural data and solved the structures. K.L., F.Y., S.T., and J.Q. analyzed the data and prepared the figures with help from D.M. and X.M. A.Z., P.H., and X.Z. performed pseudovirus-related assays. D.L. and Z.C. collected the serum samples. K.L., P.D., Q.W., and G.F.G. wrote and revised the manuscript.

We are grateful to William Ningda Gao for revising the manuscript and Hillary Yida Zhang for constructing the RaTG13 6-mutant plasmid. We are grateful to the Pathogenic Microbiology and Immunology Public Technology Service Center for its support regarding the flow cytometry assay. We acknowledge the staff of beamline BL19U1 at the Shanghai Synchrotron Radiation Facility for assistance during data collection. We also thank Y. Chen, B. Zhou, and Z. Yang from the Institute of Biophysics, Chinese Academy of Sciences, for technical support with the SPR assay. We acknowledge Z. Shi from Wuhan Institute of Virology, Chinese Academy of Sciences, for providing the ACE2 sequence of Rhinolophus affinis.

The authors declare no competing interests.

Subject:

Research Funding:

This work was supported by the Ministry of Science and Technology of the People's Republic of China; the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29010202, XDB29040203, and XDB37030204); an intramural special grant for SARS-CoV-2 research from the Chinese Academy of Sciences, National Natural Science Foundation of China (81922044), and the National Science and Technology Major Project (2018ZX10101004-001 and 2018ZX09711003-002-001). Q.W. is supported by the Youth Innovation Promotion Association of the CAS (2018119). G.F.G is supported by the Yanqi Lake Meeting organized by the academic divisions of the CAS.

Keywords:

  • ACE2
  • COVID-19
  • RBD
  • RaTG13
  • SARS-CoV-2
  • intermediate horseshoe bat
  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Monoclonal
  • Binding Sites
  • COVID-19
  • Chiroptera
  • Host Specificity
  • Humans
  • Phylogeny
  • Protein Binding
  • Receptors, Virus
  • SARS-CoV-2
  • Sequence Alignment

Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species

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Journal Title:

Cell

Volume:

Volume 184, Number 13

Publisher:

, Pages 3438-3451.e10

Type of Work:

Article | Final Publisher PDF

Abstract:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.

Copyright information:

© 2021 Elsevier Inc.

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