Efficacy of the broad-spectrum antiviral compound BCX4430 against Zika virus in cell culture and in a mouse model

Publication date: Available online 10 November 2016 Source:Antiviral Research Author(s): Justin G. Julander, Venkatraman Siddharthan, Joe Evans, Ray Taylor, Kelsey Tolbert, Chad Apuli, Jason Stewart, Preston Collins, Makda Gebre, Skot Neilson, Arnaud Van Wettere, Young-Min Lee, William P. Sheridan, John D. Morrey, Y.S. Babu Zika virus (ZIKV) is currently undergoing pandemic emergence. While disease is typically subclinical, severe neurologic manifestations in fetuses and newborns after congenital infection underscore an urgent need for antiviral interventions. The adenosine analog BCX4430 has broad-spectrum activity against a wide range of RNA viruses, including potent in vivo activity against yellow fever, Marburg and Ebola viruses. We tested this compound against African and Asian lineage ZIKV in cytopathic effect inhibition and virus yield reduction assays in various cell lines. To further evaluate the efficacy in a relevant animal model, we developed a mouse model of severe ZIKV infection, which recapitulates various human disease manifestations including peripheral virus replication, conjunctivitis, encephalitis and myelitis. Time-course quantification of viral RNA accumulation demonstrated robust viral replication in several relevant tissues, including high and persistent viral loads observed in the brain and testis. The presence of viral RNA in various tissues was confirmed by an infectious culture assay as well as immunohistochemical staining of tissu...
Source: Antiviral Therapy - Category: Virology Source Type: research