Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells. Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS coronavir...

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Bibliographic Details
Published in:	Nature Vol. 426; no. 6965; pp. 450 - 454
Main Authors:	Choe, Hyeryun, Farzan, Michael, Li, Wenhui, Moore, Michael J, Vasilieva, Natalya, Sui, Jianhua, Wong, Swee Kee, Berne, Michael A, Somasundaran, Mohan, Sullivan, John L, Luzuriaga, Katherine, Greenough, Thomas C
Format:	Journal Article
Language:	English
Published:	London Nature Publishing 27-11-2003 Nature Publishing Group Nature Publishing Group UK
Subjects:	Angiotensin converting enzyme Animals Antibodies - immunology Antibodies - pharmacology Biological and medical sciences Carboxypeptidases - antagonists & inhibitors Carboxypeptidases - genetics Carboxypeptidases - immunology Carboxypeptidases - metabolism Cell Line Chlorocebus aethiops COVID-19 Enzymes Fundamental and applied biological sciences. Psychology Genetic aspects Giant Cells - cytology Giant Cells - metabolism Humans Membrane Glycoproteins - chemistry Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Microbiology Molecular Weight Peptidyl-Dipeptidase A - immunology Peptidyl-Dipeptidase A - metabolism Protein Binding Protein Structure, Tertiary Receptors, Virus - antagonists & inhibitors Receptors, Virus - genetics Receptors, Virus - immunology Receptors, Virus - metabolism Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains SARS Virus - genetics SARS Virus - growth & development SARS Virus - metabolism Severe acute respiratory syndrome Solubility Spike Glycoprotein, Coronavirus Transfection Vero Cells Viral Envelope Proteins - chemistry Viral Envelope Proteins - genetics Viral Envelope Proteins - metabolism Virology Virus Replication - drug effects United States Virus Peptidases Coronavirus Enzyme Respiratory disease Peptidyl-dipeptidase A Hydrolases Peptidyl-dipeptidases Coronaviridae Nidovirales Biological receptor
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Summary:	Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells. Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0028-0836 1476-4687
DOI:	10.1038/nature02145