Dasabuvir (ABT-333) is a potent, selective, and nonnucleoside inhibitor of HCV NS5B polymerase with IC50 of 2.2-10.7 nM for HCV genotype 1a and 1b. Dasabuvir (ABT-333) displays >7,000-fold selective for HCV genotype 1 polymerases over human/mammalian polymerases. Dasabuvir (ABT-333) inhibits genotype 1a (strain H77) and 1b (strain Con1) replicons with EC50 values of 7.7 and 1.8 nM, respectively, with a 13-fold decrease in inhibitory activity in the presence of 40% human plasma, in HCV subgenomic replicon systems. Dasabuvir (ABT-333) retains full activity against replicons known to confer resistance to other polymerase inhibitors, including the S282T variant in the nucleoside binding site and the M423T, P495A, P495S, and V499A single variants in the thumb domain.
