The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2

Virology. 2007 Oct 25;367(2):367-74. doi: 10.1016/j.virol.2007.04.035. Epub 2007 Jul 12.


The cellular receptor for human coronavirus NL63 (HCoV-NL63), a group I coronavirus, is angiotensin-converting enzyme2 (ACE2). ACE2 is also the receptor for the SARS coronavirus (SARS-CoV), a group II coronavirus. Here we describe the ability of HCoV-NL63 to utilize a number of ACE2 variants previously characterized as SARS-CoV receptors. Several ACE2 variants that reduced SARS-CoV S-protein association similarly reduced that of HCoV-NL63, whereas alteration of a number of solvent-exposed ACE2 residues did not interfere with binding by either S protein. One notable exception is ACE2 residue 354, at the boundary of the SARS-CoV binding site, whose alteration markedly inhibited utilization by the HCoV-NL63 but not SARS-CoV S proteins. In addition, the SARS-CoV S-protein receptor-binding domain inhibited entry mediated by the HCoV-NL63 S protein. These studies indicate that HCoV-NL63, like SARS-CoV, associates region of human ACE2 that includes a key loop formed by beta-strands 4 and 5.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Binding Sites
  • Cell Line
  • Coronavirus 229E, Human / metabolism*
  • Coronavirus Infections / metabolism*
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Peptidyl-Dipeptidase A / metabolism*
  • Receptors, Cell Surface / metabolism
  • Severe acute respiratory syndrome-related coronavirus / metabolism*
  • Severe acute respiratory syndrome-related coronavirus / pathogenicity
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / metabolism*


  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV
  • spike protein, mouse hepatitis virus
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2