Abstract
2'-Methylguanosine prodrug (IDX-184), Phosphoramidate prodrug (Sofosbuvir), Diisobutyryl prodrug (R7128) are Hepatitis C Virus (HCV) Non-Structural 5B (NS5B) RNA dependent RNA polymerase (RdRp) Nucleoside Inhibitors (NI) that are currently in clinical trials. The activated forms of these Direct Acting Antiviral (DAA) drugs act on NS5B RdRp. The present work utilizes a molecular modeling approach in order to study the interaction between the activated drugs and their parent nucleotides with the 12 amino acids constituting a 5 angstrom region surrounding the active site motif GDD for HCV subtypes 1a, 2b, 3b and 4a. The analysis of their interaction energies (calculated using semi-empirical method PM3) and their vibrational properties with the polymerase suggests that their inhibitory performance likely to be more potent than native nucleotides and Ribavirin (up to date antiviral therapy).