Evaluation of the inactivation of infectious herpes simplex virus by host-defense peptides

A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide microplate a ssay was adapted to screen for the ability of 20 host-defense peptides to i nactivate herpes simplex virus type 1 and type 2. The procedure required mi nimal amounts of material, was reproducible, and was confirmed with standar d antiviral testing techniques. In screening tests, with the exception of m elittin, a highly cytotoxic and hemolytic peptide found in bee venom, the c t-helical peptides in our test panel (magainins, cecropins, clavanins, and LL-37) caused little viral inactivation. Several P-sheet peptides (defensin s, tachyplesin, and protegrins) inactivated one or both viruses, sometimes with remarkable selectivity. Two peptides were identified as having antivir al activity against both viruses, indolicidin (a tryptophan-rich peptide fr om bovine neutrophils) and brevinin-1 (a peptide found in frog skin). The a ntiviral activity of these two peptides was confirmed with standard antivir al assays. Interestingly, the antiviral activity of brevinin-1 was maintain ed after reduction and carboxamidomethylation, procedures that abolished it s otherwise prominent hemolytic and cytotoxic effects.