Dendrimers Functionalized with Membrane-Interacting Peptides for Viral Inhibition

This contribution reports the synthesis of a poly(amide)-based dendrimer functionalized at the termini with a membrane-interacting peptide derived from the Herpes Simplex virus (HSV) type 1 glycoprotein H, namely gH625-644. This peptide has been shown to interact with model membranes and to inhibit viral infectivity. The peptidodendrimer inhibits both HSV-1 and HSV-2 at a very early stage of the entry process, most likely through an interaction with the viral envelope glycoproteins; thus preventing the virus from coming into close contact with cellular membranes, a prerequisite of viral internalization. The 50% inhibitory concentration was 100 nM and 300 nM against HSV-1 and HSV-2 respectively, with no evidence of cell toxicity at these concentrations. Our results show that the functionalization of a dendrimer with the peptide sequence derived from a HSV glycoprotein shows promising inhibitory activity towards viruses of the herpesviridae family.