title: An investigative peptide-acyclovir combination to control herpes simplex virus type 1 ocular infection.
abstract: OBJECTIVE
  To investigate the efficacy of a combination treatment composed of the cationic, membrane-penetrating peptide G2, and acyclovir (ACV) in both in vitro and ex vivo models of herpes simplex virus 1 (HSV-1) ocular infection.
  
  
  METHODS
  The antiviral activity of a combined G2 peptide and ACV therapy (G2-ACV) was assessed in various treatment models. Viral entry, spread, and plaque assays were performed in vitro to assess the prophylactic efficacy of G2, G2-ACV, and ACV treatments. In the ex vivo model of HSV-1 infection, the level of viral inhibition was also compared among the three treatment groups via Western blot analysis and immunohistochemistry. The potential change in expression of the target receptor for G2 was also assessed using immunohistochemistry and RT-PCR.
  
  
  RESULTS
  Statistically significant effects against HSV-1 infection were seen in all treatment groups in the viral entry, spread, and plaque assays. The greatest effects against HSV-1 infection in vitro were seen in the G2-ACV group. In the ex vivo model, statistically significant anti-HSV-1 effects were also noted in all control groups. At 24 hours, the greatest inhibitory effect against HSV-1 infection was seen in the ACV group. At 48 hours, however, the G2-ACV-treated group demonstrated the greatest antiviral activity. Syndecan-1, a target of G2, was found to be upregulated at 12-hours postinfection.
  
  
  CONCLUSIONS
  This study shows that G2-ACV may be an effective antiviral against HSV-1 (KOS) strain when applied as single prophylactic applications with or without continuous doses postinfection.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Park
authors.forename: Thessicar E
authors.initials: TE
authors.lastname: Antoine
authors.forename: Asim V
authors.initials: AV
authors.lastname: Farooq
authors.forename: Tibor
authors.initials: T
authors.lastname: Valyi-Nagy
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage*; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage; D015153:Blotting, Western; D002460:Cell Line; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000302:isolation & purification; D007150:Immunohistochemistry; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D014709:Vero Cells
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D000998:Antiviral Agents; D000212:Acyclovir
keywords: acyclovir; heparan sulfate; herpes simplex keratitis