VX-222 (VCH-222, Lomibuvir)S14

VX-222 binds to the thumb II allosteric pocket of the HCV RNA-dependent RNA polymerase. VX-222 exhibits non-competitive and selective inhibition in HCV NS5B of genotype 1a and 1b, with IC50 of 0.94 and 1.2 μM, respectively. VX-222 selectively inhibits the replication of subgenomic HCV genotype 1a and 1b with an EC50 of 22.3 and 11.2 nM, respectively. ^[1] Similarly, a recent study shows that VX-222 inhibits the 1b/Con1 HCV subgenomic replicon, with an EC50 of 5 nM. VX-222 preferentially inhibits primer-dependent RNA synthesis, showing only a modest or no effect on de novo-initiated RNA synthesis. ^[2]