Ashraf H Abadi
Although of the success of Direct Acting Antivirals (DAAs) in the treatment of Hepatitis C Virus (HCV) there is still a room for further research and development aiming to: Discovery of more potent pan-genotypic DAA to reduce the duration of treatment, discovery of DAA with high threshold to develop resistance to allow mono therapy and not to lose the therapeutic action throughout the treatment period, expand the genotypic coverage to include GT3 which was found to be one of the hardest to treat genotypes using DAA and to develop safer DAA suitable for the treatment of HCV in children. This study describes novel small molecules that inhibit the growth of HCV in replicon assays. Several compounds showed median Effective Concentration (EC50s) in the low picomolar range and were of median cytotoxicity CC50s in the micromolar range, leading to median selectivity indices more than six orders of magnitude, which indicate their safety. Several compounds were more active than the clinically used candidate Dacaltasvir against several genotypes including GT1b, GT3 and GT4 and with lower tendency to develop resistance even after 15 weeks of continuous treatment.