Antiviral activities of 2′-deoxyribofuranosyl and arabinofuranosyl analogs of sangivamycin against retro- and DNA viruses

Eight sugar-modified pyrrolopyrimidine nucleoside analogs related to the antibiotic sangivamycin were evaluated in cell culture against herpes simplex types 1 (HSV-1) and 2 (HSV-2), cytomegalovirus (CMV), adenovirus, and visna virus. Five of the compounds were highly active against most of the viruses with 50% inhibition (ED 50) values of 1–10 μM. The selectivity of the agents was low, with inhibition of uninfected cell proliferation occurring within 5-fold that of the virus ED 50 for most of the viruses. The compounds did not possess RNA virus-inhibitory activity when evaluated against certain myxo-, paramyxo-, picorna-, reo-, rhabdo-, and togaviruses. Two of the nucleosides were tested further in a cell line persistently infected with Friend leukemia virus where they were inhibitory to both virus yield and cell proliferation at 4–5 μM. Several of the sangivamycin analogs were tested in animal models using a twice-a-day treatment regimen. They proved to be inactive against HSV-1, murine CMV and/or Friend leukemia virus infections in mice.