In silico prediction of some peroxisome proliferator-activated receptor (PPAR) agonists targeted drugs as potential SARS-Cov-2 inhibitors

Since COVID-19 epidemic began, no effective medication have been found to treat this disease. In the current study, several peroxisome proliferator-activated receptor (PPAR) agonist drugs, including fenofibrate, binifibrate, bezafibrate, ciprofibrate, clofibrate, gemfibrozil, pioglitazone, and rosiglitazone  were selected, and the molecular docking studies were applied by using main protease (Mpro), human angiotensin-converting enzyme 2 (ACE2), and transmembrane protease serine 2 (TMPRSS2) targets. The chemical structures of selected drugs were retrieved from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/). AutoDock 4.2 molecular docking program was used to obtain best binding interactions of selected drugs. Visualization of the docking results was performed using BIOVIA Discovery Studio Visualizer and PyMol. As a result, rosiglitazone and binifibrate  were found to be an effective drugs against SARS-CoV-2 main protease (MPro) with binding energies of –6.8 and -6.7 kcal/mol, respectively. Bezafibrate and binifibrate  were found to be an effective drugs against ACE2 with binding energies of –8.6 and -8.6 kcal/mol, respectively.  On the other hand, fenofibrate and bezafibrate showed highest binding energies against TMPRSS2 protein as compared  with reference drugs favipiravir, chloroquine, and hydroxychloroquine. Our in silico results suggest that PPAR agonist drugs warrant further investigation as potential lead molecules for discovering more potent compounds in anti-CoV drug development research.