Disruption of Herpes Simplex Virus Ribonucleotide Reductase Quaternary Structure by Peptide Inhibitors as a Novel Approach to Antiviral Therapy

Abstract

Peptides capable of selectively disrupting protein-pro-tein interactions that are required for viral replication represent potential agents for antiviral therapy. The first example of viral product that could be inhibited by the peptide YAGAVVNDL, targeted to the functional inter-action between subunits, is the ribonucleotide reductase of herpes simplex virus. However, this peptide alone has no effect on virally infected cells, presumably because it is too large to enter cells unaided. Escherichia coli heat-labile enterotoxin B subunit has been used as a protein carrier for the delivery of YAGAVVNDL into HSV-1 infected cells and been shown to specifically inhibit viral replication. This provides evidence of the usefulness of carrier-mediated delivery of putative antiviral peptides for the evaluation of their efficacy.