Angiotensin-converting Enzyme 2 Is a Functional Receptor for the SARS Coronavirus

Nature. 2003 Nov 27;426(6965):450-4. doi: 10.1038/nature02145.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Carboxypeptidases / antagonists & inhibitors
  • Carboxypeptidases / genetics
  • Carboxypeptidases / immunology
  • Carboxypeptidases / metabolism
  • Cell Line
  • Chlorocebus aethiops
  • Giant Cells / cytology
  • Giant Cells / metabolism
  • Humans
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • 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
  • SARS Virus / genetics
  • SARS Virus / growth & development
  • SARS Virus / metabolism*
  • Solubility
  • Spike Glycoprotein, Coronavirus
  • Transfection
  • Vero Cells
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism
  • Virus Replication / drug effects

Substances

  • Antibodies
  • MHV surface projection glycoprotein
  • Membrane Glycoproteins
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2