A-5021: a new acyclovir analogue inhibits murine herpetic keratitis

Cornea. 2008 Apr;27(3):334-8. doi: 10.1097/ICO.0b013e31815d889b.

Abstract

Purpose: To determine the efficacy of A-5021, a new analogue of acyclovir, on murine herpetic keratitis.

Methods: Herpes simplex virus type 1 (strain CHR3) was inoculated onto bilateral scarified BALB/c corneas. Clinical scores on the corneas treated with A-5021 eyedrops were compared with those obtained from the treatment with 3% acyclovir eye ointment by slit lamp microscopy. Virus titers of the trigeminal ganglia and eyeballs were quantitated on Vero cell monolayers. Mice treated with saline or a white petroleum jelly were used as controls.

Results: A-5021 eyedrops significantly suppressed both corneal epithelial and stromal lesions at all concentrations used. Clinical scores on the epithelium and stroma treated with 0.1% A-5021 were equivalent to those with 3% acyclovir treatment. When compared with the non-drug-treated control mice, virus titers in the eyeballs and trigeminal ganglia in A-5021- and acyclovir-treated mice were significantly less than those in controls.

Conclusions: A-5021 eyedrops, which are easily applied onto the affected cornea, ameliorated clinical scores and suppressed virus growth. It is a promising alternative treatment of herpetic keratitis.

MeSH terms

  • Acyclovir / analogs & derivatives*
  • Acyclovir / pharmacology
  • Animals
  • Antiviral Agents / pharmacology*
  • Chlorocebus aethiops
  • Disease Models, Animal*
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / chemistry
  • Guanine / pharmacology
  • Herpesvirus 1, Human / drug effects*
  • Herpesvirus 1, Human / physiology
  • Keratitis, Herpetic / prevention & control*
  • Keratitis, Herpetic / virology
  • Mice
  • Mice, Inbred BALB C
  • Ophthalmic Solutions / pharmacology
  • Trigeminal Ganglion / virology
  • Vero Cells / virology

Substances

  • 9-((cis-1,2-bis(hydroxymethyl)cycloprop-1-yl)methyl)guanine
  • Antiviral Agents
  • Ophthalmic Solutions
  • Guanine
  • Acyclovir