biostudies-literaturevan der Linden LNIAID NIH HHSe1004733https://www.ebi.ac.uk/biostudies/studies/S-EPMC4370873biostudies-literatureUnknown11(3)The genus Enterovirus of the family Picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71) for which no antiviral drugs are available. The viral RNA-dependent RNA polymerase is an attractive target for antiviral therapy. Nucleoside-based inhibitors have broad-spectrum activity but often exhibit off-target effects. Most non-nucleoside inhibitors (NNIs) target surface cavities, which are structurally more flexible than the nucleotide-binding pocket, and hence have a more narrow spectrum of activity and are more prone to resistance development. Here, we report a novel NNI, GPC-N114 (2,2'-[(4-chloro-1,2-phenylene)bis(oxy)]bis(5-nitro-benzonitrile)) with broad-spectrum activity against enteroviruses and cardioviruses (another gePLoS pathogensThe RNA template channel of the RNA-dependent RNA polymerase as a target for development of antiviral therapy of multiple genera within a virus family.PMC4370873R01 AI104878van Kuppeveld FJLanke KLeyssen PUlferts RDe Palma AMCoutard BCanard BLefebvre DPurstinger GFerrer-Orta CDe Clercq KArnold JJvan der Linden LLiu XSelisko BCameron CENeyts JVives-Adrian LVerdaguer NBoehr DDTanchis FGoris NLacroix CfalseThe RNA template channel of the RNA-dependent RNA polymerase as a target for development of antiviral therapy of multiple genera within a virus family.The genus Enterovirus of the family Picornaviridae contains many important human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and enterovirus 71) for which no antiviral drugs are available. The viral RNA-dependent RNA polymerase is an attractive target for antiviral therapy. Nucleoside-based inhibitors have broad-spectrum activity but often exhibit off-target effects. Most non-nucleoside inhibitors (NNIs) target surface cavities, which are structurally more flexible than the nucleotide-binding pocket, and hence have a more narrow spectrum of activity and are more prone to resistance development. Here, we report a novel NNI, GPC-N114 (2,2'-[(4-chloro-1,2-phenylene)bis(oxy)]bis(5-nitro-benzonitrile)) with broad-spectrum activity against enteroviruses and cardioviruses (another ge2015-01-01T00:00:00Z2015 Mar2026-04-08T00:46:33.141Z2019-03-26T22:43:15ZS-EPMC43708732579906410.1371/journal.ppat.1004733