Molecular Docking and Toxicity Prediction of Some Zingiber Officinale Roscoe Phytochemicals Against the Streptococcus Pneumoniae HicBA Toxin-Antitoxin Complex

Аннотация

Background: The increasing prevalence of antibiotic resistance among bacterial pathogens presents a significant global health challenge, emphasising the urgent need for novel antibacterial agents from alternative sources. Phenolic compounds like zingerone and gingerol, and sesquiterpenes like zingiberene found in Zingiber officinale (ginger) have been reported to possess antibacterial activity. In Streptococcus pneumoniae, a major respiratory pathogen, disrupting the HicBA complex could serve as an effective antibacterial strategy.

Objectives: This study aims to conduct in silico ADMET and toxicity studies of zingerone, gingerol, and zingiberene and to evaluate their inhibitory potential on the HicBA toxin-antitoxin protein complex of Streptococcus pneumoniae (PDB ID: 5YRZ) through in silico molecular docking and dynamics simulation.

Materials and Methods: Online servers, including PubChem, SWISSADME, and ProTox-II, were employed to obtain and screen the compounds. The compounds were docked using AutoDock Vina, visualized in Discovery Studio, and simulated via AMBER.

Results: The results showed that all the compounds satisfied the Lipinski’s Rule of Five, with Zingerone (MW: 194.23 g/mol, TPSA: 46.53 Ų, logP: 1.79), zingiberene (MW: 202.34 g/mol, TPSA: 0.00 Ų, logP: 4.86), and gingerol (MW: 276.37 g/mol, TPSA: 46.53 Ų, logP: 3.69), indicating favourable oral bioavailability. Toxicity predictions suggest that zingerone and zingiberene are non-toxic, while gingerol may pose a moderate risk to the kidney and respiratory systems (probability scores: 55% and 56%, respectively). Docking scores showed binding affinities of -5.5 kcal/mol (gingerol), −5.6 kcal/mol (zingerone), and -6.2 kcal/mol (zingiberene), compared to -8.7 kcal/mol for vancomycin.

Conclusion: The molecular dynamics simulation results support the possibility that zingiberene can associate with and dynamically stabilise a site on the HicBA complex. These findings suggest that zingiberene may serve as a promising lead compound for targeting the HicBA system, warranting further investigation into its potential role in modulating bacterial stress responses and persistence.