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West Nile virus (WNV) is a medically important emerging arbovirus causing serious neuroinfections in humans and against which no approved antiviral therapy is currently available. In this study, we demonstrate that 2′-C -methyl- or 4′-azido-modified nucleosides are highly effective inhibitors of WNV replication, showing nanomolar or low micromolar anti-WNV activity and negligible cytotoxicity in cell culture.

Viral RNA-Dependent RNA Polymerase Inhibitor 7-Deaza-2′- C -Methyladenosine Prevents Death in a Mouse Model of West Nile Virus Infection