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Journal of Virology, July 2009, p. 6947-6951, Vol. 83, No. 13
0022-538X/09/$08.00+0 doi:10.1128/JVI.00416-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Christine C. Yokoyama,1,
Gianmarco Orefice,1
Han-Sung Kim,1,3
Mohamed Aljofan,2
Bruce A. Mungall,1,2 and
Anne Moscona1*
Departments of Pediatrics and Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021,1 Australian Animal Health Laboratory, CSIRO Livestock Industries, 5 Portarlington Road, Geelong 3220, Australia,2 Hallym University College of Medicine, Anyang 431-070, Korea3
Received 25 February 2009/ Accepted 1 April 2009
Peptides derived from conserved heptad repeat (HR) regions of paramyxovirus fusion (F) proteins inhibit viral fusion by interfering with the formation of the fusogenic six-helix bundle structure. Peptide efficacy is affected by the strength of the peptide association with the target virus's complementary HR region. Here, we show that a second basis for peptide efficacy lies in the kinetics of F activation by the homotypic attachment protein: efficient F activation by the attachment protein shortens the period during which antiviral molecules targeting intermediate states of F may act, thereby modulating the effectiveness of inhibitory peptides. These results highlight new issues to be considered in developing strategies for fusion inhibitors.
Published ahead of print on 15 April 2009.
M.P. and C.C.Y. contributed equally.
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