Inhibition of DNA synthesis in varicella-zoster virus-infected cells by BV-araU.

The inhibitory effect of BV-araU on DNA synthesis in human embryonic lung cells infected with varicella-zoster virus (VZV) or herpes simplex virus type 1 (HSV-1) was compared with that of acyclovir. Cellular uptake of [3H]thymidine and its incorporation into DNA was markedly stimulated by the infection with VZV or HSV-1, suggesting that the incorporation was mainly due to viral DNA synthesis. DNA synthesis in VZV-infected cells was dose-dependently suppressed by BV-araU and acyclovir, although cellular uptake of [3H]thymidine decreased in cells treated with a high concentration of drugs for an extended time. DNA synthesis in HSV-1-infected cells was also markedly inhibited by both drugs in a dose-dependent manner, without affecting cellular uptake of [3H]thymidine. The concentration of drugs inhibiting DNA synthesis was well correlated to their in vitro anti-VZV and anti-HSV-1 activities. The inhibitory concentration of BV-araU for DNA synthesis in VZV-infected cells was one-thousandth of that of acyclovir. Our results suggest that the antiviral action of BV-araU against VZV and HSV-1 is based on the inhibition of DNA synthesis in herpesvirus-infected cells.     

Drug susceptibilities of isolates of varicella-zoster virus in a clinical study of oral brovavir

Susceptibilities to brovavir [1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)-uracil] and acyclovir of clinical isolates of varicella-zoster virus obtained from 58 patients with herpes zoster, included in a clinical trial of oral brovavir, were tested by a plaque reduction method. All 101 isolates were significantly susceptible to brovavir; 50% effective dose of brovavir for these isolates ranged between 0.6-4.0 ng/ml (average: 1.29 ng/ml). Brovavir was about 3,000 times more potent than acyclovir against these isolates. No marked change in the susceptibility of isolates from these patients during treatment with brovavir was observed.