Antibacterial prospects of Xylopia aethiopica against the TLP and T3SS components of Salmonella spp. through molecular docking and pharmacokinetic hybrid in silico approaches
Resistant bacteria are capable of surviving exposure to antibiotics that typically eradicate their resistance genes. This has rendered many traditional antibiotics ineffective, leaving healthcare providers with fewer options for treating infections. On this basis, medicinal plants are gradually becoming a new normal and a motivation for intensive research, including the present study. This study investigated the antibacterial potential of Xylopia aethiopica, particularly targeting the type III secretion system (T3SS) and transthyretin-like protein (TLP) of Salmonella species. This study employed hybrid in silico screening approaches involving molecular docking and pharmacokinetic investigations. The components of the plant were screened against four proteins, TLP, PrgK, SipA, and SseK. The findings of this study revealed that the components of the investigated plant can inhibit Salmonella virulence by targeting the TLP and T3SS receptors. The results of the docking analysis revealed valuable insights with a binding affinity as high as -7.4 kcal/mol, which is likely due to the interaction between andrographolide and the Salmonella-secreted effector K. Across the screened compounds, the target pockets included ARG113, THR16, HIS90, LYS18, SER92, and LYS93 for transthyretin-like proteins; GLY26, SER57, LYS48, THR59, and ASP22 for the PrgK component of the type III secretion system; LYS213, THR303, GLY302, GLY156, LEU110, ASN111, TYR143, ILE136, and ARG147 for Salmonella invasion protein A; and ARG194, ASP226, ALA227, GLN51, ARG55, ASN259, and ASP191 for the Salmonella-secreted effector K. Pharmacokinetic studies further explored andrographolide, which is the best performing compound and revealed favorable behavior based on its adsorption, distribution, metabolism, excretion, and drug likeness with zero violations of the famous drug-likeness rules, including those of Lipinski and Ghose. This study revealed that X. aethiopica and its components are good therapeutic agents, particularly for treating Salmonella infections. In vitro and in vivo studies are therefore encouraged to further unravel the intricacies and possibly the application of these components to better humans.