We studied
antiviral effects of 1-beta-D-arabinofuranosyl-5-[(E)-2-bromovinyl]
uracil (
BV-araU) and
acyclovir against varicella-zoster virus (VZV) multiplication varying the length or timing of
drug exposure. First, residual anti-VZV effect of drugs, exposed to cells for various periods followed by incubation in
drug-free medium, was determined by the plaque inhibition assay. None of the drugs showed activity when removed within 24 hr of incubation. Weakened efficacy of
BV-araU was seen in 2 days of treatment. When it was removed after 3 or 4 days, the ED50 was as low as that for cultures in which the
drug was not removed. Still, plaque inhibition was not complete even at high concentrations.
Acyclovir inhibited plaque formation only by 50% or less in 2 days of treatment. It gave a much higher ED50 in 3 days of treatment than that observed without
drug removal. In the experiments, in which
BV-araU was added to VZV-infected cells 1 day after
infection,
BV-araU immediately suppressed increase in the number of infective centers at a concentration of 0.001 microgram/ml, and reduced it at concentrations of 0.01 microgram/ml or higher. The reduction of infective centers was seen with a dose-dependent manner when added 2 or 3 days after
infection.
BV-araU stimulated the decrease in the number of infective centers when added 4 days after
infection. This inhibitory effect of
acyclovir was very weak. Microscopic observations supported the above results.
BV-araU was still much superior to
acyclovir in the anti-VZV effect when the length and timing of
drug exposure were varied.