Design,Synthesis and Discovery of N,N’-Carbazoyl-aryl-urea Inhibitors of Zika NS5 Methyltransferase and Virus Replication

摘要

The recent outbreaks of Zika virus(ZIKV)infection worldwide make the discovery of novel antivirals against flaviviruses a research priority.This work describes the identification of novel inhibitors of ZIKV through a structure-based virtual screening approach using the ZIKV NS5-MTase.A novel series of molecules with a carbazoyl-aryl-urea structure has been discovered and a library of analogues has been synthesized.The new compounds inhibit ZIKV MTase with IC_(50)between 23-48 μM.In addition,carbazoyl-aryl-ureas also proved to inhibit ZIKV replication activity at micromolar concentration.