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

• Type of Material: Article
• Authors: Kefang Liu, Institute of Microbiology Chinese Academy of Sciences; Xiaoqian Pan, Institute of Microbiology Chinese Academy of Sciences; Linjie Li, Institute of Microbiology Chinese Academy of Sciences; Feng Yu, Shanghai Advanced Research Institute, Chinese Academy of Sciences; Anqi Zheng, Institute of Microbiology Chinese Academy of Sciences; Pei Du, Institute of Microbiology Chinese Academy of Sciences; Pengcheng Han, Institute of Microbiology Chinese Academy of Sciences; Yumin Meng, Institute of Microbiology Chinese Academy of Sciences; Yanfang Zhang, Institute of Microbiology Chinese Academy of Sciences; Lili Wu, Institute of Microbiology Chinese Academy of Sciences; Qian Chen, Institute of Microbiology Chinese Academy of Sciences; Chunli Song, Anhui University; Yunfei Jia, Institute of Microbiology Chinese Academy of Sciences; Sheng Niu, Institute of Microbiology Chinese Academy of Sciences; Dan Lu, Institute of Microbiology Chinese Academy of Sciences; Chengpeng Qiao, Institute of Microbiology Chinese Academy of Sciences; Zhihai Chen, Beijing Ditan Hospital Capital Medical University; Dongli Ma, Shenzhen Children's Hospital; Xiaopeng Ma, Shenzhen Children's Hospital; Shuguang Tan, Institute of Microbiology Chinese Academy of Sciences; Xin Zhao, Institute of Microbiology Chinese Academy of Sciences; Jianxun Qi, Institute of Microbiology Chinese Academy of Sciences; George F Gao, Institute of Microbiology Chinese Academy of Sciences; Qihui Wang, Institute of Microbiology Chinese Academy of Sciences
• Language: English
• Date: 2021-06-24
• Publisher: Elsevier Inc.
• Publication Version: Final Published Version
• Copyright Statement: © 2021 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.cell.2021.05.031
• Title of Journal or Parent Work: Cell
• Volume: 184
• Issue: 13
• Start Page: 3438
• End Page: 3451.e10
• Grant/Funding Information: 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: Protein Binding; RBD; Phylogeny; Amino Acid Sequence; Animals; Binding Sites; Humans; SARS-CoV-2; Angiotensin-Converting Enzyme 2; Chiroptera; Antibodies, Monoclonal; ACE2; intermediate horseshoe bat; Sequence Alignment; Host Specificity; COVID-19; RaTG13; Receptors, Virus
• Research Categories: Health Sciences, Immunology

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.