Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE-2 in humans and other species

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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide and causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here, we obtained the complex structure of RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2), and further evaluated the binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in RaTG13 RBD with their counterparts in SARS-CoV-2 RBD, we found that residue 501, the major position found in 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 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 spill-over of CoVs.