Inhibition of Influenza A and B Viruses by 2′-Deoxy-2′-Fluororibosides

Abstract

A series of 2′-deoxy-2′-fluororibosides were evaluated for anti-influenza activity in cell culture and in the mouse pneumonia model. Many were found to be potent inhibitors of Influenza A, in chick embryo fibroblast cells (IC50's 0.1–2.9 μM), and in reducing mouse lung virus titres (1–3 log10units).Purine analogues proved the most effective, but their activity was an order of magnitude higher in MDCK cells. Anti-influenza activity correlated with intracellular triphosphate levels and with substrate specificity of 2′-deoxycytidine kinase. 2′-deoxy-2′-fluoroguanosine selected for further study was active against all influenza A and B strains tested, including one clinical isolate which proved extremely sensitive when assayed in human tracheal cultures. In vivo, 2′-deoxy-2′-fluoroguanosine (2′-fluorodGuo) was significantly more effective than amantadine or ribavirin in reducing mouse lung virus titre when treatment commenced after infection.