Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2

EMBO J. 2005 Apr 20;24(8):1634-43. doi: 10.1038/sj.emboj.7600640. Epub 2005 Mar 24.

Abstract

Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002-2003 SARS outbreak and during the much less severe 2003-2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002-2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002-2003 SARS epidemic.

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Binding Sites
  • Carboxypeptidases / chemistry
  • Carboxypeptidases / genetics
  • Carboxypeptidases / metabolism*
  • Catalytic Domain
  • Disease Outbreaks
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Peptidyl-Dipeptidase A
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • SARS Virus / metabolism*
  • Sequence Alignment
  • Severe Acute Respiratory Syndrome / epidemiology
  • Severe Acute Respiratory Syndrome / virology
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / metabolism*
  • Viverridae / virology

Substances

  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV
  • spike protein, mouse hepatitis virus
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2