Computational exploration of nigerian bioactive compounds as potential inhibitors of septic shock

Abstract

Septic shock is a fatal medical condition characterized by severe hypotension or elevated lactate levels as a consequence of sepsis. Septic shock occurs as a result of pathogenic bacterial and viral infections. In this study, twenty-eight ligands from natural plant sources were computationally screened for their ability to suppress septic shock via interaction with the protein Catechol-O-Methyltransferase (COMT) (PBD: 4XUC), as revealed by Molecular Docking, PASS, ADMET, and DFT analyses. The molecular docking results showed that the assessed ligands Capsaicine (L5) and Gingerenone A (L6) had binding affinities of -7.9 kcal/mol and -8.1 kcal/mol with an inhibition constant of 1.60 µM and 1.14 µM respectively, while the standard drugs dobutamine and dopamine had had binding affinities of -7.0 kcal/mol and -5.8 kcal/mol and inhibition constants of 7.35 µM and 55.77 µM. PASS analysis revealed that L5 and L6 had higher active probability values of 0.357 and 0.346, and the ADMET analysis ranked L5 and L6 as the best ligands. Finally, the DFT assessment showed that L5 and L6 had a band gap of 5.58 and 4.20. All the analyses showed that the two compounds , L5 and L6, had an improved binding affinity with the receptor over that of the two assessed approved drugs, dobutamine and dopamine.