tetano
Editor, Senior Moderator
Cell
. 2021 May 24;S0092-8674(21)00661-9.
doi: 10.1016/j.cell.2021.05.031. Online ahead of print.
Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species
Kefang Liu[SUP] 1 [/SUP], Xiaoqian Pan[SUP] 2 [/SUP], Linjie Li[SUP] 2 [/SUP], Feng Yu[SUP] 3 [/SUP], Anqi Zheng[SUP] 1 [/SUP], Pei Du[SUP] 1 [/SUP], Pengcheng Han[SUP] 4 [/SUP], Yumin Meng[SUP] 1 [/SUP], Yanfang Zhang[SUP] 5 [/SUP], Lili Wu[SUP] 1 [/SUP], Qian Chen[SUP] 6 [/SUP], Chunli Song[SUP] 7 [/SUP], Yunfei Jia[SUP] 8 [/SUP], Sheng Niu[SUP] 8 [/SUP], Dan Lu[SUP] 1 [/SUP], Chengpeng Qiao[SUP] 1 [/SUP], Zhihai Chen[SUP] 9 [/SUP], Dongli Ma[SUP] 10 [/SUP], Xiaopeng Ma[SUP] 10 [/SUP], Shuguang Tan[SUP] 1 [/SUP], Xin Zhao[SUP] 1 [/SUP], Jianxun Qi[SUP] 11 [/SUP], George F Gao[SUP] 12 [/SUP], Qihui Wang[SUP] 13 [/SUP]
Affiliations
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.
. 2021 May 24;S0092-8674(21)00661-9.
doi: 10.1016/j.cell.2021.05.031. Online ahead of print.
Binding and molecular basis of the bat coronavirus RaTG13 virus to ACE2 in humans and other species
Kefang Liu[SUP] 1 [/SUP], Xiaoqian Pan[SUP] 2 [/SUP], Linjie Li[SUP] 2 [/SUP], Feng Yu[SUP] 3 [/SUP], Anqi Zheng[SUP] 1 [/SUP], Pei Du[SUP] 1 [/SUP], Pengcheng Han[SUP] 4 [/SUP], Yumin Meng[SUP] 1 [/SUP], Yanfang Zhang[SUP] 5 [/SUP], Lili Wu[SUP] 1 [/SUP], Qian Chen[SUP] 6 [/SUP], Chunli Song[SUP] 7 [/SUP], Yunfei Jia[SUP] 8 [/SUP], Sheng Niu[SUP] 8 [/SUP], Dan Lu[SUP] 1 [/SUP], Chengpeng Qiao[SUP] 1 [/SUP], Zhihai Chen[SUP] 9 [/SUP], Dongli Ma[SUP] 10 [/SUP], Xiaopeng Ma[SUP] 10 [/SUP], Shuguang Tan[SUP] 1 [/SUP], Xin Zhao[SUP] 1 [/SUP], Jianxun Qi[SUP] 11 [/SUP], George F Gao[SUP] 12 [/SUP], Qihui Wang[SUP] 13 [/SUP]
Affiliations
- PMID: 34139177
- DOI: 10.1016/j.cell.2021.05.031
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.