Comparative efficacy of antiherpes drugs against various strains of varicella-zoster virus

Abstract

Twenty antiherpes compounds were compared for their inhibitory activities against five laboratory strains and five clinical isolates of varicella-zoster virus (VZV) in human embryo fibroblast cultures. E-5-(2-bromovinyl)-1-β-D-arabinofuranosyluracil (BVaraU), E-5-(2-iodovinyl)-2'-deoxyuridine (IVDU), and E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) were the most effective. The average values of the 50% inhibitory dose (ID50) for VZV replication were 0.0013, 0.0015, and 0.0024 μg.ml, respectively. 1-β-D-Arabinofuranosyladenine and 9-(2-hydroxyethoxymethyl)guanine were 1.2 and 3.4 times less effective than 5-iodo-2'-deoxyuridine (IDU). The selectivity indexes (ratio of ID50 for host-cell DNA synthesis to ID50 for VZV replication) of BVaraU, IVDU, and BVDU were between 41,000 and 67,000, whereas those of cytosine arabinoside, IDU, and 5-bromo-2'-deoxyuridine were <1.1. BVaraU, and BVDU were the most potent and the most selective inhibitors of VZV activity. A deoxythymidine kinase-deficient mutant of VZV was resistant to most of the commpounds tested at concentrations to 36,000 times greater than the average ID50 for strains that were not deficient.