A new potent inhibitor of
adenosine deaminase (
co-vidarabine) was used in combination studies with
adenine arabinoside (
vidarabine, Vira-ATM) to protect this
purine nucleoside from enzymatic deamination to the more weakly active metabolite,
hypoxanthine arabinoside. Comparing the combination to
vidarabine alone, a significant increase (10-fold) of the
antiviral activity of the combined drugs was observed against herpes and vaccinia viruses in tissue culture and subcutaneously, against cranial
herpesvirus infections in mice. Several other investigators have also recently reported several-fold enhancement of
vidarabine activity by newly described deaminase inhibitors. They observed that plaque formation by several large
DNA-containing viruses (herpes,
vaccinia,
varicella zoster) and an
RNA-containing oncogenic virus was markedly prevented by the combination compared to
vidarabine alone. In animals, enhanced protection (increased survivors) and/or highly significant increase in the life span of dying mice treated with the 2-drug combination, was also observed compared to
vidarabine administered singly. These observations in animals clearly indicate that combination studies with
vidarabine (Vira-ATM) and
co-vidarabine (deaminase inhibitor) deserve serious consideration as future
therapy for systemic
virus infections in man including herpesvirus
encephalitis.