Efficacy and selectivity of some nucleoside analogs as anti-human cytomegalovirus agents

Abstract

1-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC), 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluridine (FMAU), 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouridine (FIAU), and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-ethyluridine (FEAU) were evaluated for antiviral activities against human cytomegalovirus (HCMV) and compared with 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) and E-5-(2'-bromovinyl)-2'-deoxyuridine (BVDU). The relative anti-HCMV potencies of these compounds, as determined by calculating the dose of drug which inhibited 50% plaque formation, were in order of decreasing potency: FIAC greater than FIAU greater than FMAU greater than acyclovir greater than FEAU greater than BVDU. The antiviral activity of FIAC occurred at levels much lower than those that caused cytotoxic or cytostatic effects in uninfected fibroblasts. Neither thymidine nor deoxycytidine reversed the anti-HCMV activity of FIAC, indicating that this drug was not acting as an analog of the natural nucleosides. FIAC was not phosphorylated by cytosols of HCMV-infected cells to a greater extent that by those of uninfected cells, indicating that, unlike the antiviral activity against herpes simplex virus type 1, the selectivity of this drug is probably not based on a virus-specified pyrimidine kinase.