Abstract
Enterococcus Faecalis poses a significant clinical challenge as it can form persistent biofilms and exhibits multidrug resistance, with the Enterococcal surface protein (Esp) acting as a vital virulence factor for stabilizing biofilms. A computational approach was used to identify small-molecule inhibitors that selectively target the Esp N-terminal domain to disrupt biofilm formation and decrease virulence. Using the Esp crystal structure, molecular docking simulations with AutoDock 4.2 and AutoDock Vina identified lead compounds such as Myricetin and Quercetin dihydrate, which demonstrated high binding affinities. Extensive virtual screening and ADMET profiling with SwissADME confirmed that these lead compounds possess favourable drug-like qualities and pharmacokinetic properties, including high gastrointestinal absorption and adherence to Lipinski's Rule of Five. This in silico study successfully highlights a set of potential lead compounds as novel anti-virulence agents.
