Kinetic dependence of paramyxovirus entry inhibition.
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.
Department of Pediatrics, Weill Medical College of Cornell University, New York, New York 10021, USA.
Matteo
M
Porotto
Christine C
CC
Yokoyama
Gianmarco
G
Orefice
Han-Sung
HS
Kim
Mohamed
M
Aljofan
Bruce A
BA
Mungall
Anne
A
Moscona
D015707:HN Protein / Q000378:metabolism; D007700:Kinetics; D018098:Paramyxovirinae / Q000502:physiology*; D010455:Peptides / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014760:Viral Fusion Proteins / Q000378:metabolism*; D053586:Virus Internalization
D015707:HN Protein; D010455:Peptides; D014760:Viral Fusion Proteins