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DOI	10.1073/pnas.2025373118
	Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2
	Liu Y.; Hu G.; Wang Y.; Ren W.; Zhao X.; Ji F.; Zhu Y.; Feng F.; Gong M.; Ju X.; Zhu Y.; Cai X.; Lan J.; Guo J.; Xie M.; Dong L.; Zhu Z.; Na J.; Wu J.; Lan X.; Xie Y.; Wang X.; Yuan Z.; Zhang R.; Ding Q.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	The pandemic of COVID-19, caused by SARS-CoV-2, is a major global health threat. Epidemiological studies suggest that bats (Rhinolophus affinis) are the natural zoonotic reservoir for SARS-CoV-2. However, the host range of SARS-CoV-2 and intermediate hosts that facilitate its transmission to humans remain unknown. The interaction of coronavirus with its host receptor is a key genetic determinant of host range and cross-species transmission. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as the receptor to enter host cells in a species-dependent manner. In this study, we characterized the ability of ACE2 from diverse species to support viral entry. By analyzing the conservation of five residues in two virus-binding hotspots of ACE2 (hotspot 31Lys and hotspot 353Lys), we predicted 80 ACE2 proteins from mammals that could potentially mediate SARS-CoV-2 entry. We chose 48 ACE2 orthologs among them for functional analysis, and showed that 44 of these orthologs—including domestic animals, pets, livestock, and animals commonly found in zoos and aquaria—could bind the SARS-CoV-2 spike protein and support viral entry. In contrast, New World monkey ACE2 orthologs could not bind the SARS-CoV-2 spike protein and support viral entry. We further identified the genetic determinant of New World monkey ACE2 that restricts viral entry using genetic and functional analyses. These findings highlight a potentially broad host tropism of SARS-CoV-2 and suggest that SARS-CoV-2 might be distributed much more widely than previously recognized, underscoring the necessity to monitor susceptible hosts to prevent future outbreaks. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	COVID-19 \| SARS-CoV-2 \| ACE2 \| host range \| intermediate host
语种	英语
scopus关键词	angiotensin converting enzyme 2; coronavirus spike glycoprotein; dipeptidyl carboxypeptidase; protein binding; spike protein, SARS-CoV-2; virus receptor; Article; binding site; coronavirus disease 2019; enzyme activity; host range; human; human cell; molecular evolution; molecular genetics; nonhuman; phylogeny; Platyrrhini; priority journal; protein binding; protein protein interaction; Severe acute respiratory syndrome coronavirus 2; species diversity; viral tropism; virus cell interaction; virus entry; virus transmission; animal; genetics; host range; metabolism; pandemic; prevention and control; veterinary medicine; virology; virus attachment; Angiotensin-Converting Enzyme 2; Animals; COVID-19; Host Specificity; Humans; Pandemics; Peptidyl-Dipeptidase A; Phylogeny; Protein Binding; Receptors, Virus; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Viral Tropism; Viral Zoonoses; Virus Attachment; Virus Internalization
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180200
作者单位	Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, 100084, China; Key Laboratory of Medical Molecular Virology, Biosafety Level 3 Laboratory, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China; School of Life Sciences, Tsinghua University, Beijing, 100084, China; Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, 310024, China; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, 310024, China; Beijing Advanced Innovation Center for Structural Biology, Tsinghua University, Beijing, 100084, China
推荐引用方式 GB/T 7714	Liu Y.,Hu G.,Wang Y.,et al. Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2[J],2021,118(12).
APA	Liu Y..,Hu G..,Wang Y..,Ren W..,Zhao X..,...&Ding Q..(2021).Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Liu Y.,et al."Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).