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 >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 >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.Research on the antiviral effects of cationic polypeptides began appearing in literature more than 30 years ago (2,(8)(9)(10)19). In early studies, investigators examined the effect of different molecular species of poly-L-lysine polypeptides on a variety of viruses. The viruses studied included tobacco mosaic, mumps, Newcastle disease, and influenza, and although inhibitory effects were noted in both tissue culture and animal studies, poly-L-lysine has since been determined to be toxic in mammalian systems (1,4,27,28).In our laboratory, we have been examining the antifungal properties of synthetic homologous histidine polypeptides (24, 25) because of their structural and functional resemblance to a unique family of naturally occurring histidinerich polypeptides secreted by the human salivary glands (17,24,26). In the course of our investigations into the spectrum of antimicrobial activities of these synthetic histidine peptides, we have observed that poly-L-histidine of appropriate chain length and molecular weight can directly and irreversibly inactivate herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). plemented with 5% calf serum, 50 ,ug of gentamicin per ml, and 0.075% NaHCO3.Laboratory strains of HSV-1 and HSV-2 were used throughout. The type designation of each virus was authenticated by indirect monoclonal antibody immunofluorescence (31), restriction endonuclease patterns (20), and sensitivity to (E)-5-(2-bromovinyl)-2'-deoxyuridine (5).Poly-amino acids. Homologous polypeptides of L-histidine containing 12 (His-12), 18 (His-18), and 24 (His-24) amino acid residues wi...

Inhibition of Herpes Simplex Virus by Polyamines

“…This contradicts the results obtained with poly-L-histidine, where anti-herpesvirus activity was pH-dependent. In brief, the ability of histidine peptides to inhibit the infectivity of HSV was influenced by the total cationic charge of the imidazole side chain of the histidine residue at an appropriate pH [17]. Additional studies are required in order to explain the unpredicted inactivity of the monoquaternary ammonium-based conjugate.…”

“…In addition, an inhibitory effect of poly-l-lysine on other viruses, like tobacco mosaic virus, which causes viral envelope disruption, has been reported by Burger and Stahmann [16]. Docherty and Pollock [17] showed that poly-l-histidine conjugates inactivate HSV-1 and HSV-2 at pH 5 and 6 by 99%. A similar effect was obtained with poly-l-arginine, which inhibited HSV-1 and HSV-2 at all pH levels tested, whereas poly-l-lysine demonstrated a weaker effect on these viruses [17].…”

“…Docherty and Pollock [17] showed that poly-L-histidine conjugates inactivate HSV-1 and HSV-2 at pH 5 and 6 by 99%. A similar effect was obtained with poly-L-arginine, which inhibited HSV-1 and HSV-2 at all pH levels tested, whereas poly-L-lysine demonstrated a weaker effect on these viruses [17].…”

Instantaneous Inactivation of Herpes Simplex Virus by Silicon Nitride Bioceramics

“…These include antiviral medications and physical or chemical treatments [ 8 , 9 ]. A number of antiviral medications have been proposed for the treatment of Herpes virus infections [ 10 , 11 , 12 , 13 ]. Among these, medications referred to as acyclovir, valacyclovir, and famciclovir work by inhibiting the viral DNA replication process [ 14 ].…”

Further studies on the antiviral activity of alloferon and its analogues

“…In this investigation, we would like to shed some light on the role of the His residue at position 1 of the alloferon peptide chain on the antiviral activity. These studies were inspired by the opinion presented in the literature that the presence of a His residue in the peptide chain of a suitable structure may endow such a peptide with potent antiviral capabilities15. At the same time, we performed these studies because the role of the basic amino acids at position 1 has not been sufficiently established in the previous investigations of the structure–biological function relationship3.…”