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. Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Kinetic dependence of paramyxovirus entry inhibition

Porotto, Matteo;
2009

Abstract

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. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11591/388675
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