Molecular modeling and docking revealed superiority of IDX-184 as HCV polymerase inhibitor

Abstract

Aim: IDX-184 is a nonstructural 5b nucleoside inhibitor (NI) that was under clinical trials against HCV. This work adopts a molecular modeling approach in order to study the interaction between IDX-184 and HCV polymerase from four different genotypes. Methods: Comparisons to the native nucleotide (Guanosine triphosphate) and other NIs were performed using interaction descriptors, calculated using semiempirical quantum mechanics and molecular docking. Results: IDX-184 shows potent binding to the active site of the polymerases. In addition, IDX-184 was better than Sofosbuvir and Ribavirin when docked into polymerase active site (even with experimentally solved structure). Conclusion: Analysis of the interaction descriptors and docking complexes suggests IDX-184 as a superior NI against the studied HCV subtypes.