Testing small molecule inhibitors of Zika virus RNA polymerase

Zika Virus (ZIKV) is a mosquito-transmitted virus capable of causing of severe neurological disease and neurocognitive disorders in infected adults and infants. From 2015 to 2016, a major outbreak in Brazil resulted in an estimated 1.5 million zika infections and at least 3,500 infants born with zika-related microcephaly or other symptoms of congenital zika syndrome. Presently, no vaccines or antivirals exist to treat ZIKV infection. The ZIKV RNA-dependent RNA polymerase (RdRp) enzyme is critical to replication of the single-stranded RNA virus and has previously been the target of in silico screening of a library of 100,000 small molecules for their potential to interfere with virus replication. We tested the seven lead compounds from this in silico screening for their ability to inhibit virus replication in cell-based in vitro assays. Compound 50 demonstrated high antiviral activity in infected cell cultures at a concentration 1.5 μM. Compound 50 has an (IC50) of 5.8 μM and a CC50 of no less than 60 μM, giving it a relatively high selectivity index of 10.4 and demonstrating its strong potential as an anti-ZIKV drug candidate.