Peptides containing membrane-interacting motifs inhibit herpes simplex virus type 1 infectivity.
Herpes simplex virus (HSV) membrane fusion represents an attractive target for anti-HSV therapy. To investigate the structural basis of HSV membrane fusion and identify new targets for inhibition, we have investigated the different membranotropic domains of HSV-1 gH envelope glycoprotein. We observed that fusion peptides when added exogenously are able to inhibit viral fusion likely by intercalating with viral fusion peptides upon adopting functional structure in membranes. Interestingly, peptides analogous to the predicted HSV-1 gH loop region inhibited viral plaque formation more significantly. Their inhibitory effect appears to be a consequence of their ability to partition into membranes and aggregate within them. Circular dichroism spectra showed that peptides self-associate in aqueous and lipidic solutions, therefore the inhibition of viral entry may occur via peptides association with their counterpart on wild-type gH. The antiviral activity of HSV-1 peptides tested provides an attractive basis for the development of new fusion peptide inhibitors corresponding to regions outside the fusion protein heptad repeat regions.
Department of Biological Sciences, Division of Biostructures, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.
Stefania
S
Galdiero
Annarita
A
Falanga
Mariateresa
M
Vitiello
Marina
M
D'Isanto
Marco
M
Cantisani
Aikaterini
A
Kampanaraki
Ettore
E
Benedetti
Helena
H
Browne
Massimiliano
M
Galdiero
D000595:Amino Acid Sequence; D000818:Animals; D002522:Chlorocebus aethiops; D002942:Circular Dichroism; D019295:Computational Biology; D004591:Electrophoresis, Polyacrylamide Gel; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000472:pathogenicity; D008561:Membrane Fusion / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000737:chemistry*
D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C044200:glycoprotein H, herpes simplex virus type 1