Screening and activity analysis of ZIKV RdRp inhibitors

The epidemic of Zika virus (ZIKV) raises critical public health and safety problems. However, there are currently no vaccines or drugs that are clinically approved for ZIKV infections. Since RNA-dependent RNA polymerase (RdRp) plays an important role in replication and transcription of ZIKV and is absent in human beings, it is a potential drug screening target of anti-ZIKV agents. According to the fluorescence-based alkaline phosphatase-coupled polymerase assay method, we established the NS5 RdRp inhibitor screening model. Through screening from an anti-infection compound library, we found a compound octenidine dihydrochloride (OCT) that could inhibit ZIKV RdRp activity with a half maximal inhibitory concentration (IC₅₀) of 5.43 μmol·L^-1. Biolayer interferometry (BLI) assay showed that OCT could bind to ZIKV RdRp and had a strong affinity. Moreover, OCT exhibited an inhibitory effect on ZIKV replication with a half maximal effective concentration (EC₅₀) of 29.94 μmol·L^-1. All these results indicated that OCT had the anti-ZIKV activity by targeting ZIKV RdRp, and it is likely to be a promising lead compound against ZIKV.