Zika Viral Polymerase: a promising therapeutic target

Abstract

Zika virus, a member of the Flaviviridae family, has garnered global attention due to the link of recent outbreaks with increased risk of fetal microcephaly and Guillan‐Barré syndrome in adults. As of yet, there are no approved therapies for treatment or prevention of Zika virus. In this research, we analyze inhibition of Zika virus replication by nucleoside analogs – a therapeutic strategy that has been successful levied against other members of the Flaviviridae family. We have recombinantly expressed and purified the RNA‐dependent RNA polymerase (RdRP) domain of the ZIKV NS5 protein. The purified protein is used in an in vitro primer extension assay to characterize incorporation of native nucleotides and inhibitory analogs opposite a Zika specific template. Of a pool of nucleoside analogs, we have identified a compound that incorporates at approximately 1/5 the rate of native nucleoside. We plan to combine biochemical, cellular, and animal model studies to determine efficacy of these compounds in inhibiting Zika viral replication and infection.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.