Molecular Docking, Dynamics Simulation, ADMET Profiling and DFT Reveal Anti-HCV Properties of Newly Discovered Catenulopyrizomicin A and B

Background The hepatitis C virus (HCV) has no vaccine, and available medications present with adverse outcomes. A recent study reported potential anti-virus activity for the newly discovered catenulopyrizomicin A and B using non-in silico methods. Method In this study, the anti-HCV potential of catenulopyrizomicin A and B were evaluated using in silico approaches (molecular docking, simulation, ADMET profiling, and DFT) using ribavirin as a control and 5EQS as the target protein (NS3/4A). Results Docking scores for the ligands were − 5.8, -5.8, and − 6.1 kcal/mol, respectively, for catenulopyrizomicin B, ribavirin, and catenulopyrizomicin A. Two dimensional (2D) visualisation of the formed complexes revealed the dominance of Van der Waals forces and polar interactions between the ligands and the target protein. Docking simulations revealed variations in the simulation parameters (RMSD and RMSF) that indicated that the formed stables complexes (less than 2.0 Å), and this was further supported by low RMSF values that were less than 2.0 Å throughout the docking simulation runs. ADMET properties revealed that catenulopyrizomicin A and B had better intestinal absorption rates (36.41% and 36.28%) than ribavirin (30.95%), as well as good distribution, as revealed by their better VDss values (-0.53 to -0.61 for catenulopyrizomicin A and B) compared to ribavirin which was − 0.22. The DFT results showed that catenulopyrizomicin A and B are more reactive and nucleophilic than ribavirin. Conclusion Overall, the study showed that catenulopyrizomicin A and B possess potential anti-HCV properties that require further in vivo and in vitro evaluations.