Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infectivity by peptides analogous to the viral spike protein

Virus Res. 2006 Sep;120(1-2):146-55. doi: 10.1016/j.virusres.2006.03.001. Epub 2006 Apr 17.

Abstract

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the cause of an atypical pneumonia that affected Asia, North America and Europe in 2002-2003. The viral spike (S) glycoprotein is responsible for mediating receptor binding and membrane fusion. Recent studies have proposed that the carboxyl terminal portion (S2 subunit) of the S protein is a class I viral fusion protein. The Wimley and White interfacial hydrophobicity scale was used to identify regions within the CoV S2 subunit that may preferentially associate with lipid membranes with the premise that peptides analogous to these regions may function as inhibitors of viral infectivity. Five regions of high interfacial hydrophobicity spanning the length of the S2 subunit of SARS-CoV and murine hepatitis virus (MHV) were identified. Peptides analogous to regions of the N-terminus or the pre-transmembrane domain of the S2 subunit inhibited SARS-CoV plaque formation by 40-70% at concentrations of 15-30 microM. Interestingly, peptides analogous to the SARS-CoV or MHV loop region inhibited viral plaque formation by >80% at similar concentrations. The observed effects were dose-dependent (IC50 values of 2-4 microM) and not a result of peptide-mediated cell cytotoxicity. The antiviral activity of the CoV peptides tested provides an attractive basis for the development of new fusion peptide inhibitors corresponding to regions outside the fusion protein heptad repeat regions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Hemagglutinins / chemistry
  • Hemagglutinins, Viral / chemistry*
  • Membrane Glycoproteins / chemistry*
  • Molecular Sequence Data
  • Murine hepatitis virus / chemistry
  • Peptides / chemical synthesis
  • Peptides / genetics
  • Peptides / pharmacology*
  • Protein Subunits / chemical synthesis
  • Protein Subunits / genetics
  • Protein Subunits / pharmacology
  • SARS Virus / drug effects*
  • SARS Virus / growth & development
  • SARS Virus / pathogenicity
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / chemistry*
  • Viral Plaque Assay
  • Virulence / drug effects

Substances

  • Hemagglutinins
  • Hemagglutinins, Viral
  • MHV surface projection glycoprotein
  • Membrane Glycoproteins
  • Peptides
  • Protein Subunits
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike glycoprotein, SARS-CoV