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

ABSTRACT

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 (ED50) values of 1-10 microM. The selectivity of the agents was low, with inhibition of uninfected cell proliferation occurring within 5-fold that of the virus ED50 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 microM. 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.