Inactivation of herpes simplex virus types 1 and 2 by synthetic histidine peptides

Abstract

Synthetic homologous histidine peptides were found to directly and irreversibly inactivate herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). The inactivation, which occurred within 1 min of virus exposure to the drug, was independent of temperature but dependent upon the pH and molecular size of the polypeptide. Poly-L-histidine consisting of 24 residues (His-24), with a molecular weight (m.w.) of 3,310, inactivated greater than 99% of the virus present at pH 6.0 and 62% at pH 5.0. Poly-L-histidine consisting of 64 (His-64; average m.w., 8,800) or 75 residues (His-75; average m.w., 10,300) inactivated greater than 99% of virus present at pH 5.0 and 6.0. However, His-24, -64, and -75 were not active against these viruses at pH 7.0 or 8.0. At the concentrations tested, poly-L-histidine of 12 (His-12; m.w., 1,665) or 18 (His-18; m.w., 2,487) residues had no effect on HSV-1 or HSV-2 at any of the pHs tested. When these studies were repeated with other basic homologous polypeptides, poly-L-arginine and poly-L-lysine, various degrees of inactivation were observed that were most pronounced in the neutral-to-alkaline pH range. Once virus was inactivated by poly-L-histidine, the effect could not be reversed in vitro by raising the pH to 7.2 or in vivo by injecting the virus into the neutral environment of an animal. These data suggest that the presence of histidine residues in a peptide of suitable structure may endow that peptide with potent antiviral capabilities.