Human cytomegalovirus (HCMV)
infection can lead to congenital
hearing loss and
mental retardation. Upon immune suppression, reactivation of latent HCMV or primary
infection increases morbidity in
cancer,
transplantation, and late stage
AIDS patients. Current treatments include
nucleoside analogues, which have significant toxicities limiting their usefulness. In this study we screened a panel of synthetic
heparin-binding
peptides for their ability to prevent CMV
infection in vitro. A
peptide designated, p5+14 exhibited ~ 90% reduction in murine CMV (MCMV)
infection. Because negatively charged, cell-surface
heparan sulfate proteoglycans (HSPGs), serve as the attachment receptor during the adsorption phase of the CMV
infection cycle, we hypothesized that p5+14 effectively competes for CMV adsorption to the cell surface resulting in the reduction in
infection. Positively charged Lys residues were required for
peptide binding to cell-surface HSPGs and reducing
viral infection. We show that this inhibition was not due to a direct neutralizing effect on the virus itself and that the
peptide blocked adsorption of the virus. The
peptide also inhibited
infection of other herpesviruses: HCMV and herpes simplex virus 1 and 2 in vitro, demonstrating it has broad-spectrum
antiviral activity. Therefore, this
peptide may offer an adjunct
therapy for the treatment of herpes
viral infections and other viruses that use HSPGs for entry.