Drug Repurposing for Vancomycin-Resistant Enterococcus faecalis (V583): A Structure-Based Virtual Screening Approach

Bacterium Enterococcus faecalis that has shown resistance against Vancomycin (V583) happens to pose serious threats on the clinical front as it is resistive to the last line of antibiotics drugs. This study looks like a structure-based virtual screening of the predicted inhibitors for AhpF C503A mutant form of the bacteria E. faecalis. Such refinement would improve a model that uses the PDB-REDO server which brings down R-free from 22.1% to 19.6% while improving stereochemical accuracy. The refined structure was validated for computational screening by using ProSA, Ramachandran plot analysis, and Verify3D. The receptor-based virtual screening from DrugRep FDA approved drug identified the following compounds with high binding affinity as top-three candidates: Venetoclax (-10.2 kcal/mol), Rimegepant (-9.7 kcal/mol) and Lumacaftor (-9.5 kcal/mol). Key interactions consist of hydrogen bond formations and hydrophobic contacts, as evidenced by the molecular docking analysis within these active sites. Such findings provide potential drug repurposing candidates for E. faecalis infections and part of the foundation for further molecular dynamics simulations and experimental validation.