<i>In silico</i> screening of <i>Thymus vulgaris</i> phytochemicals as multi-target inhibitors against <i>Staphylococcus aureus</i> biofilms in osteomyelitis

Abstract Background : Staphylococcus aureus poses a significant global health threat, particularly through severe infections like osteomyelitis, a chronic bone disease marked by inflammation, bone destruction, and necrosis. The rise of antibiotic-resistant S. aureus strains and their ability to form biofilms significantly complicate therapeutic management. Methods : Molecular docking was performed using AutoDock Vina, followed by binding site validation with CBDock2. Pharmacokinetic properties were assessed using SwissADME, and structural stability of selected complexes was evaluated through root mean square fluctuation (RMSF)-based molecular dynamics simulations using CABSflex2.0. Results : Phytochemicals from Thymus vulgaris , recognised for their antimicrobial and anti-inflammatory properties, were screened as potential inhibitors of S. aureus . The phytochemicals of T. vulgaris showed binding affinities of −4 to −8.0 kcal/mol with an average of −6 kcal/mol against key proteins. ADMET analysis indicated favourable drug-likeness profiles for most compounds, particularly for key resistant targets, supporting sustained binding stability. Conclusion : Trans-caryophyllene and bisabolene demonstrated strong multi-target binding affinities and stable molecular dynamics profiles with drug-likeness properties. These findings support further experimental validation through in vitro antimicrobial assays, biofilm inhibition studies, and in vivo osteomyelitis models to confirm their therapeutic potential against MDR S. aureus .