In silico assessment of catenulopyrizomicin A and B as potential inhibitors of HCV NS3/4A protease

The hepatitis C virus (HCV) has no vaccine, and available therapies are linked to adverse outcomes, high costs and emergence of resistance. A previous study have identified catenulopyrizomicin A and B as bioactive compounds from natural products with reported antiviral properties, warranting further evaluation against the HCV NS3/4A protease using non-in silico methods. The aim of this study was to evaluate the anti-HCV potentials of catenulopyrizomicins A and B against 5EQS, a genotype 1a/3a chimeric HCV NS3/4A protease of HCV using in silico approaches. In this study, the anti-HCV potential of catenulopyrizomicin A and B was evaluated using in silico approaches (molecular docking, simulation, ADMET profiling, and DFT) with ribavirin as a control, and 5EQS as the target protein (NS3/4A). 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. Molecular dynamics simulations revealed variations in RMSD and RMSF that indicated that the formed stable complexes with values that remained below 2.0 Å throughout most of the simulation runs, indicating stability. Ligand-protein contact analysis revealed the presence of conserved residues, including Gln1041, Thr1042, His1057, Arg1109, Leu1132, Leu1135, Lys1136, and Cys1159 across the test ligands, suggesting that they may be important in ligand recognition and foramtion of stable interactions. 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 were more reactive and nucleophilic than ribavirin. The findings suggest that catenulopyrizomicin A and B may serve as potential lead compounds for anti-HCV drug development. However, further in vitro and in vivo studies are required to validate their antiviral activity and pharmacological properties.