title: Infectivity inhibition by overlapping synthetic peptides derived from the gH/gL heterodimer of herpes simplex virus type 1.
abstract: Herpes simplex virus (HSV) is a human pathogen that infects epithelial cells. The cutaneous lesions, caused by the virus, spread to the nervous system creating several complications. Fusion of host membranes with the viral envelope is mandatory and mediated by a group of glycoproteins conserved in all Herpesviridae subfamilies, such as the glycoproteins B (gB), H (gH), L (gL) and D (gD). We investigated the inhibitory activity mediated by synthetic overlapping peptides spanning the entire ectodomains of gH and gL glycoproteins. We have performed a brute analysis of the complete gH/gL heterodimer in order to explore the inhibitory activity of peptides modelled on these glycoproteins against HSV-1 infection. Twenty-four of the gH peptides at a concentration of 150 μM reached the 50% of inhibition cut-off. Interestingly, they are mainly located in the gH carboxy-terminal domain. None of the gL peptides had a clear inhibiting effect. No peptide toxicity was observed by lactate dehydrogenase assay at the concentrations used in our experimental conditions. HSV-1 therapy is based on acyclovir treatment, but some resistant strains are emerging. In this scenario, innovative approaches for HSV-1 treatment are necessary. Our data support the direct involvement of the described domains in the process of virus penetration; therefore, these results are of relevance to the potential development of novel therapeutic compounds to prevent HSV-1 infections. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via De Crecchio 7, 80138, Naples, Italy.|Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples 'Federico II', Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Franci
authors.affiliation: Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples 'Federico II', Via Mezzocannone 16, 80134, Naples, Italy.|Department of Pharmacy, University of Naples 'Federico II', Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Annarita
authors.initials: A
authors.lastname: Falanga
authors.affiliation: Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via De Crecchio 7, 80138, Naples, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Zannella
authors.affiliation: Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via De Crecchio 7, 80138, Naples, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Folliero
authors.affiliation: Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via De Crecchio 7, 80138, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Martora
authors.affiliation: Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via De Crecchio 7, 80138, Naples, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Galdiero
authors.affiliation: Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples 'Federico II', Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Galdiero
authors.affiliation: Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples 'Federico II', Via Mezzocannone 16, 80134, Naples, Italy.|Department of Pharmacy, University of Naples 'Federico II', Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli
authors.affiliation: Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via De Crecchio 7, 80138, Naples, Italy.|Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, University of Naples 'Federico II', Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Galdiero
mesh_terms: D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000737:chemistry; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000821:virology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006023:Glycoproteins; D010455:Peptides
keywords: herpes simplex virus; infectivity inhibition; overlapping peptides; viral glycoprotein