tetano
Editor, Senior Moderator
EMBO J
. 2022 Dec 15;e111737.
doi: 10.15252/embj.2022111737. Online ahead of print.
Host range and structural analysis of bat-origin RshSTT182/200 coronavirus binding to human ACE2 and its animal orthologs
Yu Hu[SUP] #[/SUP][SUP] 1 2 [/SUP], Kefang Liu[SUP] #[/SUP][SUP] 2 [/SUP], Pu Han[SUP] 2 [/SUP], Zepeng Xu[SUP] 3 [/SUP], Anqi Zheng[SUP] 2 4 [/SUP], Xiaoqian Pan[SUP] 2 4 [/SUP], Yunfei Jia[SUP] 2 5 [/SUP], Chao Su[SUP] 2 6 [/SUP], Lingfeng Tang[SUP] 3 [/SUP], Lili Wu[SUP] 2 [/SUP], Bin Bai[SUP] 2 4 [/SUP], Xin Zhao[SUP] 2 [/SUP], Tian Di[SUP] 7 [/SUP], Zhihai Chen[SUP] 7 [/SUP], Jianxun Qi[SUP] 2 4 [/SUP], Qihui Wang[SUP] 2 4 [/SUP], George F Gao[SUP] 1 2 4 [/SUP]
Affiliations
Abstract
Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2 and show identical receptor binding domains (RBDs). In this study, we determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. Binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 out of 39 ACE2 orthologs, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2. Furthermore, RshSTT182 pseudovirus could utilize human, fox and Rhinolophus affinis ACE2 receptors for cell entry. Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus. Taken together, the findings indicate that RshSTT182/200 can potentially infect susceptible animals, but requires further evolution to obtain strong interspecies transmission abilities like SARS-CoV-2.
Keywords: ACE2; RBD; RshSTT182/200; SARS-CoV-2; interspecies transmission.
. 2022 Dec 15;e111737.
doi: 10.15252/embj.2022111737. Online ahead of print.
Host range and structural analysis of bat-origin RshSTT182/200 coronavirus binding to human ACE2 and its animal orthologs
Yu Hu[SUP] #[/SUP][SUP] 1 2 [/SUP], Kefang Liu[SUP] #[/SUP][SUP] 2 [/SUP], Pu Han[SUP] 2 [/SUP], Zepeng Xu[SUP] 3 [/SUP], Anqi Zheng[SUP] 2 4 [/SUP], Xiaoqian Pan[SUP] 2 4 [/SUP], Yunfei Jia[SUP] 2 5 [/SUP], Chao Su[SUP] 2 6 [/SUP], Lingfeng Tang[SUP] 3 [/SUP], Lili Wu[SUP] 2 [/SUP], Bin Bai[SUP] 2 4 [/SUP], Xin Zhao[SUP] 2 [/SUP], Tian Di[SUP] 7 [/SUP], Zhihai Chen[SUP] 7 [/SUP], Jianxun Qi[SUP] 2 4 [/SUP], Qihui Wang[SUP] 2 4 [/SUP], George F Gao[SUP] 1 2 4 [/SUP]
Affiliations
- PMID: 36519268
- DOI: 10.15252/embj.2022111737
Abstract
Bat-origin RshSTT182 and RshSTT200 coronaviruses (CoV) from Rhinolophus shameli in Southeast Asia (Cambodia) share 92.6% whole-genome identity with SARS-CoV-2 and show identical receptor binding domains (RBDs). In this study, we determined the structure of the RshSTT182/200 receptor binding domain (RBD) in complex with human angiotensin-converting enzyme 2 (hACE2) and identified the key residues that influence receptor binding. Binding of the RshSTT182/200 RBD to ACE2 orthologs from 39 animal species, including 18 bat species, was used to evaluate its host range. The RshSTT182/200 RBD broadly recognized 21 out of 39 ACE2 orthologs, although its binding affinities for the orthologs were weaker than those of the RBD of SARS-CoV-2. Furthermore, RshSTT182 pseudovirus could utilize human, fox and Rhinolophus affinis ACE2 receptors for cell entry. Moreover, we found that SARS-CoV-2 induces cross-neutralizing antibodies against RshSTT182 pseudovirus. Taken together, the findings indicate that RshSTT182/200 can potentially infect susceptible animals, but requires further evolution to obtain strong interspecies transmission abilities like SARS-CoV-2.
Keywords: ACE2; RBD; RshSTT182/200; SARS-CoV-2; interspecies transmission.