4′-Azidocytidine (R1479) inhibits henipaviruses and other paramyxoviruses with high potency

•Cytidine analog 4′-azidocytidine (R1479) exhibits in vitro antiviral activity against multiple paramyxoviruses.•R1479 is most potent against Nipah virus, but exhibits similar activity against all paramyxoviruses tested.•R1479 exemplifies the potential for developing a broad-spectrum 4′-modified nucleoside analog therapeutic.

The henipaviruses Nipah virus and Hendra virus are highly pathogenic zoonotic paramyxoviruses which have caused fatal outbreaks of encephalitis and respiratory disease in humans. Despite the availability of a licensed equine Hendra virus vaccine and a neutralizing monoclonal antibody shown to be efficacious against henipavirus infections in non-human primates, there remains no approved therapeutics or vaccines for human use. To explore the possibility of developing small-molecule nucleoside inhibitors against henipaviruses, we evaluated the antiviral activity of 4′-azidocytidine (R1479), a drug previously identified to inhibit flaviviruses, against henipaviruses along with other representative members of the family Paramyxoviridae. We observed similar levels of R1479 antiviral activity across the family, regardless of virus genus. Our brief study expands the documented range of viruses susceptible to R1479, and provides the basis for future investigation and development of 4'-modified nucleoside analogs as potential broad-spectrum antiviral therapeutics across both positive and negative-sense RNA virus families.