In vitro susceptibility of varicella-zoster virus to E-5-(2-bromovinyl)-2'-deoxyuridine and related compounds.
The in vitro susceptibility of eight strains of varicella-zoster virus (VZV) to E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) was examined in human embryonic fibroblasts by the following techniques: inhibition of focus formation by either cell-free VZV (4-day assay) or cell-associated VZV (2-day assay), inhibition of viral antigen formation (2-day assay), and inhibition of viral cytopathogenicity (15-day assay). The 50% inhibitory dose (ID50) of BVDU ranged from 0.001 microgram/ml (2-day assay) to 0.01 microgram/ml (15-day assay). BVDU appeared highly selective in its anti-VZV activity since even at concentrations as high as 100 micrograms/ml, BVDU did not markedly affect the viability of the host cells. The ID50 of BVDU for VZV was comparable to that of IVDU (E-5-(2-iodovinyl)-2'-deoxyuridine). Both drugs inhibited the replication of VZV at a much lower concentration than did other antiviral compounds such as iododeoxyuridine, ethyldeoxyuridine, arabinosylcytosine, arabinosyladenine, phosphonoacetic acid, iododeoxycytidine, and acycloguanosine. BVDU and IVDU were virtually inactive against a thymidine kinase-deficient VZV mutant, suggesting that phosphorylation by the viral enzyme is responsible, at least in part, for the selective anti-VZV activity of the compounds.
D000998:Antiviral Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D006562:Herpes Zoster / Q000188:drug therapy; D014645:Herpesvirus 3, Human / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D010766:Phosphorylation
D000998:Antiviral Agents; C020235:brivudine; D001973:Bromodeoxyuridine