Molecular docking, dynamics and experimental approach integrated identification of phytopharmaceuticals against...

Methicillin-resistant Staphylococcus aureus (MRSA) is indeed a significant public health issue, affecting millions of people worldwide which can range from mild skin infections to life-threatening conditions like bloodstream infections and pneumonia. The aim of the current study is to decipher the possible mechanism of some selected natural compounds against MRSA. The natural compounds were selected based on our earlier systematic literature review. The selected compounds were screened against various targets of MRSA using molecular docking techniques. The stability of selected compounds was checked using molecular dynamics. Further, Absorption, Distribution, Metabolism and Excretion (ADME) was predicted using QikProp module. All the computational studies were conducted using the Schrodinger Maestro version 13.5.128. In-vitro assays were conducted to check the anti-bacterial effects of selected natural compounds against MRSA. Among 60 selected natural compounds, theasinensin A, xanthohumol, luteolin, oxyresveratrol, liquiritigenin and baicalin has shown the energetically favoured binding conformation in the active site of targets. Further, molecular dynamics results have shown the stable conformation of xanthohumol and theasinensin A in the active site of targets. Further, the pharmacokinetic profile of xanthohumol was found to be better among other natural compounds. The minimum inhibitory concentration (MIC) of xanthohumol was found to be 3.12 µg/mL as indicated by disk diffusion and micro broth dilution assays. Xanthohumol can be promising anti-bacterial agent against MRSA through multi modal mechanism. However, further detailed experimental studies are required to confirm its possible antibacterial mechanisms.