Abstract
Enterovirus 71 (EV71) has emerged as an important virulent neurotropic enterovirus in young children. DTriP-22 was found to be a novel and potent inhibitor of EV71. The molecular target of this compound was identified by analyzing DTriP-22-resistant viruses. A substitution of lysine for Arg163 in the EV71 3D polymerase rendered the virus drug-resistant. DTriP-22 exhibited the ability to inhibit viral replication by reducing viral RNA accumulation. The compound suppressed the accumulated levels of both viral positive- and negative-stranded RNA during virus infection. In vitro polymerase assay indicated that DTriP-22 inhibited the poly(U) elongation activity, but not VPg uridylylation activity, of EV71 polymerase. These findings demonstrate that a non-nucleoside analogue, DTriP-22, acts as a novel inhibitor of EV71 polymerase. DTriP-22 also exhibited a broad-spectrum of antiviral activity against other picornaviruses, which highlights its potential in the development of antiviral agents.