NOVEL MEFENAMIC ACID-ANTIBIOTIC COMBINATIONS AS POTENTIAL INHIBITORS OF SARS-COV-2 MAIN PROTEASE
DOI:
https://doi.org/10.22159/ijpps.2026v18i2.57105Keywords:
COVID-19, Mefenamic acid, Antibiotics, Molecular docking, ADME properties, Main protease (Mpro)Abstract
Objective: The ongoing search for effective COVID-19 treatments has driven interest in drug repurposing and hybrid drug design strategies. This study aimed to develop and evaluate novel mefenamic acid–antibiotic hybrids as potential inhibitors of the SARS-CoV-2 main protease (Mpro).
Methods: Eight hybrid molecules were rationally designed and analyzed using molecular docking and in silico ADME evaluations to predict their binding affinity, stability, pharmacokinetic, and pharmacodynamic behaviour.
Results: Eight mefenamic acid–antibiotic hybrids were evaluated for their potential to inhibit SARS-CoV-2 Mpro. All hybrids demonstrated stronger binding affinity than mefenamic acid (MEF) alone, with the MEF–cephalexin (MEF–CEX) conjugate showing the most favorable binding energy (–7.6 kcal/mol), indicating enhanced complex stability due to the cephalosporin scaffold. ADME predictions revealed moderate pharmacokinetic properties across the series, and the MEF–ciprofloxacin (MEF–CIP) hybrid displayed notable blood–brain barrier permeability despite one Lipinski rule violation.
Conclusion: The findings highlight mefenamic acid–antibiotic hybrids, particularly cephalosporin-based derivatives, as promising multifunctional candidates with combined anti-inflammatory and antiviral potential against SARS-CoV-2. Further preclinical validation is warranted to optimize their pharmacological and safety profiles for potential therapeutic application.
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