A pan-serotype dengue virus inhibitor targeting the NS3-NS4B interaction

Dengue virus causes approximately 96 million symptomatic infections annually,manifesting as dengue fever or occasionally as severe dengue1,2.There are no antiviral agents available to prevent or treat dengue.Here,we describe a highly potent dengue virus inhibitor(JNJ-A07)that exerts nanomolar to picomolar activity against a panel of 21 clinical isolates that represent the natural genetic diversity of known genotypes and serotypes.The molecule has a high barrier to resistance and prevents the formation of the viral replication complex by blocking the interaction between two viral proteins(NS3 and NS4B),thus revealing a previously undescribed mechanism of antiviral action.