DOI: 10.1016/j.scib.2021.01.011
论文题名: The Rhinolophus affinis bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2
作者: Li P. ; Guo R. ; Liu Y. ; Zhang Y. ; Hu J. ; Ou X. ; Mi D. ; Chen T. ; Mu Z. ; Han Y. ; Chen Z. ; Cui Z. ; Zhang L. ; Wang X. ; Wu Z. ; Wang J. ; Jin Q. ; Qian Z.
刊名: Science Bulletin
ISSN: 20959273
出版年: 2021
卷: 66, 期: 12 起始页码: 1215
结束页码: 1227
语种: 英语
中文关键词: Bat coronavirus RaTG13
; Coronavirus entry
; Host susceptibility
; Rhinolophus affinis bat ACE2
; SARS-CoV-2
; Spike protein
英文关键词: Animals
; Diseases
; Viruses
; Angiotensin-converting enzyme 2
; Bat coronavirus ratg13
; Coronavirus entry
; Coronaviruses
; Host susceptibility
; Rhinolophu affini bat ACE2
; Severe acute respiratory syndrome coronavirus
; Severe acute respiratory syndrome coronavirus 2
; Spike protein
; Virus entry
; Proteins
英文摘要: Bat coronavirus (CoV) RaTG13 shares the highest genome sequence identity with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among all known coronaviruses, and also uses human angiotensin converting enzyme 2 (hACE2) for virus entry. Thus, SARS-CoV-2 is thought to have originated from bat. However, whether SARS-CoV-2 emerged from bats directly or through an intermediate host remains elusive. Here, we found that Rhinolophus affinis bat ACE2 (RaACE2) is an entry receptor for both SARS-CoV-2 and RaTG13, although the binding of RaACE2 to the receptor-binding domain (RBD) of SARS-CoV-2 is markedly weaker than that of hACE2. We further evaluated the receptor activities of ACE2s from additional 16 diverse animal species for RaTG13, SARS-CoV, and SARS-CoV-2 in terms of S protein binding, membrane fusion, and pseudovirus entry. We found that the RaTG13 spike (S) protein is significantly less fusogenic than SARS-CoV and SARS-CoV-2, and seven out of sixteen different ACE2s function as entry receptors for all three viruses, indicating that all three viruses might have broad host rages. Of note, RaTG13 S pseudovirions can use mouse, but not pangolin ACE2, for virus entry, whereas SARS-CoV-2 S pseudovirions can use pangolin, but not mouse, ACE2 enter cells efficiently. Mutagenesis analysis revealed that residues 484 and 498 in RaTG13 and SARS-CoV-2 S proteins play critical roles in recognition of mouse and human ACE2s. Finally, two polymorphous Rhinolophous sinicus bat ACE2s showed different susceptibilities to virus entry by RaTG13 and SARS-CoV-2 S pseudovirions, suggesting possible coevolution. Our results offer better understanding of the mechanism of coronavirus entry, host range, and virus-host coevolution. © 2021 Science China Press Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/170315
Appears in Collections: 气候变化与战略
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作者单位: NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100176, China; School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250062, China; The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, 100084, China
Recommended Citation:
Li P.,Guo R.,Liu Y.,et al. The Rhinolophus affinis bat ACE2 and multiple animal orthologs are functional receptors for bat coronavirus RaTG13 and SARS-CoV-2[J]. Science Bulletin,2021-01-01,66(12)