Naringenin as a Promising Phytotherapeutic Scaffold Against MRSA: Molecular Docking and ADMET Profiling Study
Abstract
Antimicrobial resistance has emerged globally, leading to the increased need to seek alternative therapeutic scaffolds to treat the Methicillin-resistant Staphylococcus aureus (MRSA). Naringenin, a flavanone compound of citrus fruit, has antimicrobial and anti-inflammatory effects, and thus is a potential phytotherapeutic agent. The aim of the study was to determine the potential of naringenin to interact with MRSA at the molecular level as well as have a pharmacokinetic profile through molecular docking and in silico ADMET analysis. The molecular docking of the MRSA target protein (PDB ID: 6O9S) to assess binding affinity and patterns of interaction was performed using UCSF Chimera. Clindamycin was taken as a standard. The profiles of ADMET were determined on ADMETlab 3.0 and ADMET-AI to evaluate the drug-likeness, absorption, distribution, metabolism, excretion and toxicity parameters. Naringenin had a higher binding affinity (-7.5 kcal/mol) than clindamycin (-6.5 kcal/mol). Analyzing of interaction indicated optimization of hydrophobic interaction with key residues (PHE423, TRP426, TYR438, ILE533, GLY530) and stable hydrogen bonding especially with TRP426. The compound had a lower molecular flexibility which implied a lower entropic penalty when binding. The analysis of ADMET made it possible to verify adherence to the Rule of Five developed by Lipinski, high absorption in the intestine (0.95), good Caco-2 permeability, and minimal chances of hepatotoxicity and cardiotoxicity. Nonetheless, the predictions borderline mutagenicity and genotoxicity suggest that more experiments are required. Naringenin has good binding stability and good pharmacokinetic properties in comparison to the normal antibiotic, which indicates a promising candidate of phytotherapeutic scaffold to develop anti-MRSA drugs.
Keywords: Naringenin; Methicillin-resistant Staphylococcus aureus [MRSA]; Molecular Docking; ADMET; Phytotherapeutic; Antimicrobial Resistance
Keywords:
Naringenin, Methicillin-resistant Staphylococcus aureus [MRSA], Molecular Docking, ADMET, Phytotherapeutic, Antimicrobial ResistanceDOI
https://doi.org/10.22270/jddt.v16i7.7880References
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Copyright (c) 2026 Vinay Kumar Yadav , Vikash Singh , Brij Raj Singh , Vikas Kumar , Amita Verma
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