International Journal of Drug Delivery Technology
Volume 15, Issue 2

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

Sanjivani Panditkar1, Machchhindra Holam2, Satish Dhonde3, Tushar Fegade4*

1Department of Applied Chemistry, Yashwantrao Chavan College of Engineering, Affiliated to Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, India

2Department of Pharmaceutical Chemistry, Sant Gajanan Maharaj College of Pharmacy, Mahagaon, Affiliated to Shivaji University, Kolhapur, Maharashtra, India

3Department of Pharmacology, SVNH College of B.Pharmacy, Rahuri, Ahilyanagar, Affiliated to Savitribai Phule Pune University, Pune, Maharashtra, India

4Department of Pharmaceutics, Shellino Education Society’s Arunamai College of Pharmacy, Mamurabad, Affiliated to Kavayitri Bahinabai Chaudhari North Maharashtra University, Jalgaon, Maharashtra, India 

Received: 29th Dec, 2024; Revised: 19th Mar, 2025; Accepted: 21st Apr, 2025; Available Online: 25th Jun, 2025

ABSTRACT

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.

Keywords: Vancomycin-resistant Enterococcus faecalis, drug repurposing, structure-based virtual screening, AhpF C503A, molecular docking, PDB-REDO, antimicrobial resistance, FDA-approved drugs

How to cite this article: Sanjivani Panditkar, Machchhindra Holam, Satish Dhonde, Tushar Fegade. Drug Repurposing for Vancomycin-Resistant Enterococcus Faecalis (V583): A Structure-Based Virtual Screening Approach. International Journal of Drug Delivery Technology. 2025;15(2):510-18. doi: 10.25258/ijddt.15.2.19

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