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.