Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides

DOI Web Site 被引用文献3件
  • Berend Jan Bosch
    Divisions of Virology and Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands; Department of Virology, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France; and Department of Biomolecular Mass Spectrometry, Bijvoet Centre for Biomolecular Research and...
  • Byron E. E. Martina
    Divisions of Virology and Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands; Department of Virology, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France; and Department of Biomolecular Mass Spectrometry, Bijvoet Centre for Biomolecular Research and...
  • Ruurd van der Zee
    Divisions of Virology and Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands; Department of Virology, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France; and Department of Biomolecular Mass Spectrometry, Bijvoet Centre for Biomolecular Research and...
  • Jean Lepault
    Divisions of Virology and Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands; Department of Virology, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France; and Department of Biomolecular Mass Spectrometry, Bijvoet Centre for Biomolecular Research and...
  • Bert Jan Haijema
    Divisions of Virology and Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands; Department of Virology, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France; and Department of Biomolecular Mass Spectrometry, Bijvoet Centre for Biomolecular Research and...
  • Cees Versluis
    Divisions of Virology and Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands; Department of Virology, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France; and Department of Biomolecular Mass Spectrometry, Bijvoet Centre for Biomolecular Research and...
  • Albert J. R. Heck
    Divisions of Virology and Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands; Department of Virology, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France; and Department of Biomolecular Mass Spectrometry, Bijvoet Centre for Biomolecular Research and...
  • Raoul de Groot
    Divisions of Virology and Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands; Department of Virology, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France; and Department of Biomolecular Mass Spectrometry, Bijvoet Centre for Biomolecular Research and...
  • Albert D. M. E. Osterhaus
    Divisions of Virology and Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands; Department of Virology, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France; and Department of Biomolecular Mass Spectrometry, Bijvoet Centre for Biomolecular Research and...
  • Peter J. M. Rottier
    Divisions of Virology and Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands; Department of Virology, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands; Virologie Moléculaire et Structurale, Centre National de la Recherche Scientifique, 91190 Gif-sur-Yvette, France; and Department of Biomolecular Mass Spectrometry, Bijvoet Centre for Biomolecular Research and...

抄録

<jats:p>The coronavirus SARS-CoV is the primary cause of the life-threatening severe acute respiratory syndrome (SARS). With the aim of developing therapeutic agents, we have tested peptides derived from the membrane-proximal (HR2) and membrane-distal (HR1) heptad repeat region of the spike protein as inhibitors of SARS-CoV infection of Vero cells. It appeared that HR2 peptides, but not HR1 peptides, were inhibitory. Their efficacy was, however, significantly lower than that of corresponding HR2 peptides of the murine coronavirus mouse hepatitis virus (MHV) in inhibiting MHV infection. Biochemical and electron microscopical analyses showed that, when mixed, SARS-CoV HR1 and HR2 peptides assemble into a six-helix bundle consisting of HR1 as a central triple-stranded coiled coil in association with three HR2 α-helices oriented in an antiparallel manner. The stability of this complex, as measured by its resistance to heat dissociation, appeared to be much lower than that of the corresponding MHV complex, which may explain the different inhibitory potencies of the HR2 peptides. Analogous to other class I viral fusion proteins, the six-helix complex supposedly represents a postfusion conformation that is formed after insertion of the fusion peptide, proposed here for coronaviruses to be located immediately upstream of HR1, into the target membrane. The resulting close apposition of fusion peptide and spike transmembrane domain facilitates membrane fusion. The inhibitory potency of the SARS-CoV HR2-peptides provides an attractive basis for the development of a therapeutic drug for SARS.</jats:p>

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