title: Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2.
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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, MA 01772-9102, USA.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.forename: Chengsheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Sui
authors.forename: Jens H
authors.initials: JH
authors.lastname: Kuhn
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Shiwen
authors.initials: S
authors.lastname: Luo
authors.forename: Swee-Kee
authors.initials: SK
authors.lastname: Wong
authors.forename: I-Chueh
authors.initials: IC
authors.lastname: Huang
authors.forename: Keming
authors.initials: K
authors.lastname: Xu
authors.forename: Natalya
authors.initials: N
authors.lastname: Vasilieva
authors.forename: Akikazu
authors.initials: A
authors.lastname: Murakami
authors.forename: Yaqing
authors.initials: Y
authors.lastname: He
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Marasco
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.forename: Hyeryun
authors.initials: H
authors.lastname: Choe
authors.forename: Michael
authors.initials: M
authors.lastname: Farzan
mesh_terms: D000595:Amino Acid Sequence; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain; D004196:Disease Outbreaks; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D016415:Sequence Alignment; D045169:Severe Acute Respiratory Syndrome / Q000453:epidemiology / Q000821:virology; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000378:metabolism*; D045949:Viverridae / Q000821:virology
chemical_list: D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2