Discovery of Inhibitors Targeting the RNA-Dependent RNA Polymerase of the Zika Virus

The Zika virus (ZIKV) is a Orthoflavivirus linked to several neurological and developmental diseases, and it remains a significant global health threat for which no treatments or vaccines are currently available. In this study, we optimized the malachite green colorimetric assay, previously used to measure the RNA-dependent RNA polymerase (RdRp) activity of the hepatitis C and foot- and-mouth disease viruses, and applied this assay to identify inhibitors of ZIKV RdRp, an enzyme essential for viral replication. Inhibitor screening was conducted using 204 compounds from the Natural Product Set IV of the National Cancer Institute Developmental Therapeutics Program. We identified two compounds, purpurogallin and digallic acid, as inhibitors of ZIKV RdRp. Future studies will characterize the potency and elucidate the mechanisms of action of these compounds.