Flavonoid derivatives from red propolis: In silico predictions of their interactions with Staphylococcus aureus sortase A and studies on their antibiofilm potential

Sortase A (SrtA) is an enzyme essential for biofilm formation in Gram-positive bacteria including Staphylococcus aureus. In silico investigations were conducted to investigate the interactions of flavonoid derivatives from red propolis with S. aureus SrtA (PDB ID:1T2P). Molecular docking, MD and ADME/drug-likeness predictions used Autodock Vina, GROMACS-2021 and SwissADME, respectively. Chrysin, galangin, thevetiaflavone and vestitone showed the best size-independent ligand efficiency (SILE) scores–higher than those of the control ligand. The chrysin- and thevetiaflavone-protein complexes showed the most stable behaviour and compactness in MD analysis. Chrysin and thevetiaflavone exhibited high binding free energy values towards SrtA. Chrysin interacted strongly with eight active site residues (including two from the catalytic triad) while thevetiaflavone interacted with four active site residues (including one from the catalytic triad). An in vitro crystal violet staining assay confirmed that chrysin and galangin showed significant antibiofilm activity against S. aureus. It remains to be seen if thevetiaflavone displays any similar activity. Further studies are warranted to confirm if the binding of these flavonoids to sortase A is a possible mechanism of their antibiofilm activity. As such, they may prove useful for the discovery of new antibiofilm agents against S. aureus.