Synthetic analogues of bovine bactenecin dodecapeptide reduce herpes simplex virus type 2 infectivity in mice

Abstract

We have evaluated the potential of four synthetic peptides (denoted HH-2, 1002, 1006, 1018) with a distant relationship to the host defense peptide bovine bactenecin dodecapeptide for their ability to prevent genital infections with herpes simplex virus type 2 (HSV-2) in mice. All four peptides showed antiviral properties in vitro and reduced HSV-2 infection of Vero cells in a dose-dependent manner. Detailed analysis showed that the peptides were able to interfere with both viral attachment and entry, but not with replication post-entry, and were effective antivirals also when HSV-2 was introduced in human semen. Two of the peptides proved especially effective in reducing HSV-2 infection also in vivo. When admixed with virus prior to inoculation, both HH-2 and 1018 reduced viral replication and disease development in a genital model of HSV-2 infection in mice, and also when using very high infectious doses of HSV-2. These data show that peptides HH-2 and 1018 have antiviral properties and can be used to prevent genital herpes infection in mice.

Keywords: AMPs; Antimicrobial peptides; Bovine bactenecin; GAG; Genital herpes; HDPs; HNP; HS; HSV-2; Synthetic analogues; anti-microbial peptides; glycosaminoglycans; heparan sulfate; herpes simplex virus type 2; host defense peptides; human neutrophil peptides.