JTK-109

JTK-109 is a small molecule antiviral drug developed by Japan Tobacco that acts as a potent non-nucleoside inhibitor of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. As a benzimidazole derivative, it binds to the Thumb I allosteric site of the NS5B polymerase, effectively blocking viral replication with high potency against genotypes 1b and 3a. Although its clinical development for HCV was discontinued, JTK-109 has demonstrated significant broad-spectrum activity against various caliciviruses, including norovirus, sapovirus, and lagovirus. This activity is mediated by targeting a highly conserved pocket, known as Site-B, within the thumb domain of the viral RNA-dependent RNA polymerase (RdRp).