Repurposing Entacapone, a Catechol-O-Methyl ...

Repurposing Entacapone, a Catechol-O-Methyl Transferase Inhibitor, for Alcohol Use Disorder: A Combined Morgan Fingerprint and Docking Approach

Author Name : Mr. Adivarekar Shonak Sandeep, Dr. Udugade Babaso.Vithal

DOI: https://doi.org/10.56025/IJARESM.2024.121024499

ABSTRACT This study investigates the potential of repurposing Entacapone, a known catechol-O-methyl transferase (COMT) inhibitor, for the treatment of Alcohol Use Disorder (AUD) using an integrated approach that combines Morgan Fingerprint analysis and molecular docking studies. Entacapone, originally approved for managing Parkinson’s disease, was identified as a candidate through ligand-based virtual screening on the DrugRep platform. The screening revealed a strong binding affinity of Entacapone to aldehyde dehydrogenase (ALDH), with a docking score of -8.3, suggesting its potential to inhibit this enzyme, similar to the mechanism of action seen with Disulfiram, a commonly used AUD medication. Molecular docking studies further highlighted key interactions between Entacapone and critical residues in ALDH, providing a structural basis for its repurposing in AUD therapy. Validation metrics from PDB-REDO showed notable improvements in model quality, with reductions in the R-free value from 0.2772 to 0.2490, and enhancements in bond angle RMS Z scores and Ramachandran plot normality, further supporting the robustness of the docking results. This study underscores the feasibility of using Entacapone as a potential therapeutic agent for AUD and highlights the utility of combining ligand-based screening with molecular docking in drug repurposing. The findings pave the way for further experimental validation and potential clinical applications for AUD treatment, especially in patients seeking alternative therapeutic options.