gms | German Medical Science

International Conference on SARS - one year after the (first) outbreak

08. - 11.05.2004, Lübeck

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SARS-CoV infection inhibition using spike protein heptad repeat-derived peptides

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  • corresponding author presenting/speaker Berend Jan Bosch - Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  • Byron Martina - Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  • Ruurd van der Zee - Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  • Bert Jan Haijema - Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  • Raoul de Groot - Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  • Albert Osterhaus - Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  • Peter Rottier - Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

International Conference on SARS - one year after the (first) outbreak. Lübeck, 08.-11.05.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04sars9.02

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/sars2004/04sars047.shtml

Veröffentlicht: 26. Mai 2004

© 2004 Bosch et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.

Gliederung

Text

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 heptad repeat region (HR1) 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 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 alpha-helices oriented in an anti-parallel 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 post-fusion 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.