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Anti-herpesvirus activity of adenine arabinoside analogues in tissue culture and a genital infection of mice and guinea pigs.

Abstract
Four analogues of adenine arabinoside (ara-A) were compared for activity against herpes simplex virus (HSV) in tissue culture and in a genital infection of mice and guinea pigs. These analogues, 5'-monophosphate (ara-AMP), 5'-valerate ester (ara-AV), 2'3'-diacetate ester (ara-ADA), and 2',3',5'- triacetate ester (ara-ATA) have greater water and lipid solubility and resistance to deamination than ara-A. In mouse embryo fibroblast cells, similar viral inhibitory levels were noted with ara-A, AMP, and ara-Av, while ara-ADA and ara-ATA were 6-10 time less active. In mice infected intravaginally with HSV type 2 (HSV-2), intravaginal treatment with 10% concentrations of each of the compounds beginning 3 h after viral challenge, had no effect on infection rates, titers of virus in vaginal secretions, mortality rates or the mean day of death as compared with placebo-treated controls. In the HSV-2 genital infection of guinea pigs, treatment with 10% vaginal creams or placebo vehicle was initiated 6 or 24 h after viral inoculation. In animals treated at 6 h with ara-A, ara-AMP and ara-AV, there was complete inhibition of viral replication in the vaginal tract and development of external genital lesions. When treatment with these three drugs was delayed 24 h after infection, there was no effect on vaginal virus titers, but lesions severity was reduced by ara-A or ara-AMP therapy. Ara-ATA was ineffective whether begun at 6 or 24 h. The greater solubility in water and lipid as well as the resistance to deamination of ara-AMP and ara-AV did not appear to enhance their antiviral activity over that of ara-A. Additionally, ara-ADA and ara-ATA exhibited less activity both in tissue culture and in the experimental genital infections.
AuthorsJ T Richards, E R Kern, J C Overall Jr, L A Glasgow
JournalAntiviral research (Antiviral Res) Vol. 2 Issue 1-2 Pg. 27-39 (May 1982) ISSN: 0166-3542 [Print] Netherlands
PMID6179469 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Vidarabine Phosphate
  • vidarabine 2',3',5'-triacetate
  • vidarabine 2',3'-diacetate
  • vidarabine 5'-valerate
  • Vidarabine
Topics
  • Administration, Topical
  • Animals
  • Culture Techniques
  • Drug Evaluation, Preclinical
  • Female
  • Fibroblasts
  • Guinea Pigs
  • Herpes Genitalis (drug therapy)
  • Male
  • Mice
  • Simplexvirus (drug effects, growth & development)
  • Vidarabine (analogs & derivatives, pharmacology)
  • Vidarabine Phosphate (pharmacology)

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