Integrated Bioinformatic Modeling of Goniothalamin as a Dual-target Medicinal Chemistry Candidate against Antibiotic-resistant Staphylococcus aureus and Escherichia coli

The emergence of antimicrobial resistance (AMR) highlights the need for innovative chemical scaffolds that disrupt bacterial virulence and replication mechanisms. Goniothalamin is a styryl lactone with some potential, but its molecular mechanisms on clinical pathogens are still unknown. The goal of this study was to establish the feasibility of goniothalamin as a medicinal chemistry lead through the study of its interactions with the key bacterial proteins, agrA and ftsZ, using molecular docking.

Target prediction was performed using SEA Search. Functional roles and virulence were assessed using VICMPred and VirulentPred. Molecular docking for binding affinities was performed using SwissDock/AutoDock Vina, and immunogenicity was assessed via reverse vaccinology (IEDB). Selectivity was tested against human JAK2.

Goniothalamin had high affinity values for S. aureus agrA (-4.935 kcal/mol) and E. coli ftsZ (-4.739 kcal/mol). Interactions were primarily stabilized through a dense network of hydrophobic contacts. Reverse vaccinology exposed several highly antigenic epitopes, including the MKIFICEDDPKQREN peptide (score = 0.9061).

The way goniothalamin interacts with molecules shows it achieves stability by fitting securely into the non-polar spaces of its targets. By blocking a part of the agrA protein, this compound could work as an agent that reduces the virulence of pathogens without putting too much pressure on the pathogens to develop resistance. At the same time, its ability to trigger a strong immune response suggests it could be used in combination with other methods to prevent infections.

Goniothalamin is a promising dual-target anti-virulence and replication-inhibitory structural class for rational drug design against MDR pathogens.