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

Kefang Liu; Xiaoqian Pan; Linjie Li; Feng Yu; Anqi Zheng; Pei Du; Pengcheng Han; Yumin Meng; Yanfang Zhang; Lili Wu; Qian Chen; Chunli Song; Yunfei Jia; Sheng Niu; Dan Lu; Chengpeng Qiao; Zhihai Chen; Dongli Ma; Xiaopeng Ma; Shuguang Tan; Xin Zhao; Jianxun Qi; George F Gao; Qihui Wang

doi:10.1016/j.cell.2021.05.031

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

Cell. 2021 Jun 24;184(13):3438-3451.e10. doi: 10.1016/j.cell.2021.05.031. Epub 2021 May 24.

Authors

Kefang Liu¹, Xiaoqian Pan², Linjie Li², Feng Yu³, Anqi Zheng¹, Pei Du¹, Pengcheng Han⁴, Yumin Meng¹, Yanfang Zhang⁵, Lili Wu¹, Qian Chen⁶, Chunli Song⁷, Yunfei Jia⁸, Sheng Niu⁸, Dan Lu¹, Chengpeng Qiao¹, Zhihai Chen⁹, Dongli Ma¹⁰, Xiaopeng Ma¹⁰, Shuguang Tan¹, Xin Zhao¹, Jianxun Qi¹¹, George F Gao¹², Qihui Wang¹³

Affiliations

¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
² CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
³ Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China.
⁴ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Department of Biomedical Engineering, Emory University, Atlanta, GA 10033, USA.
⁵ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.
⁶ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Institute of Physical Science and Information, Anhui University, Hefei 230039, China.
⁷ Institute of Physical Science and Information, Anhui University, Hefei 230039, China.
⁸ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China.
⁹ Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, 100015 Beijing, China.
¹⁰ Shenzhen Children's Hospital, Shenzhen 518036, China.
¹¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: jxqi@im.ac.cn.
¹² CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: gaof@im.ac.cn.
¹³ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address: wangqihui@im.ac.cn.

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.

Keywords: ACE2; COVID-19; RBD; RaTG13; SARS-CoV-2; intermediate horseshoe bat.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Angiotensin-Converting Enzyme 2 / metabolism*
Animals
Antibodies, Monoclonal / immunology
Binding Sites / physiology*
COVID-19 / immunology
COVID-19 / metabolism*
Chiroptera / immunology
Chiroptera / metabolism
Chiroptera / virology*
Host Specificity / immunology
Humans
Phylogeny
Protein Binding / physiology
Receptors, Virus / metabolism
SARS-CoV-2 / immunology
SARS-CoV-2 / pathogenicity*
Sequence Alignment

Substances

Antibodies, Monoclonal
Receptors, Virus
ACE2 protein, human
Angiotensin-Converting Enzyme 2