TMC647055 is a novel and potent nonnucleoside the HCV NS5B RNA-dependent RNA polymerase inhibitor. TMC647055 shows high selectivity for HCV when evaluated with a broad panel of human DNA and RNA viruses. TMC647055 shows median EC50 changes in the replicon assay of 9-, 3-, and 371-fold for L392I, V494A, and P495L, respectively, The median EC50 of TMC647055 on NS5B sequences derived from clinical isolates of genotypes 1a, 1b, 3a, 4a, and 6a ranged between 27 nM and 113 nM.