Format

Send to

Choose Destination
EMBO J. 2005 Apr 20;24(8):1634-43. Epub 2005 Mar 24.

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

Author information

1
Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, MA 01772-9102, USA.

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.

PMID:
15791205
PMCID:
PMC1142572
DOI:
10.1038/sj.emboj.7600640
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center