Effect of BV-araU and acyclovir on varicella-zoster virus replication with various length and timing of drug exposure.
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.
Machida
H
H
Biology Laboratory, R & D Division, Yamasa Corporation, Chiba, Japan.
Nishitani
M
M
Ashida
N
N
D000212:Acyclovir / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage*; D001086:Arabinofuranosyluracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D014645:Herpesvirus 3, Human / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D006801:Humans; D013997:Time Factors; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D001086:Arabinofuranosyluracil; C031368:sorivudine; D000212:Acyclovir