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A computational effort to untangling anti-SARS-CoV-2 effects of oleanolic acid analogues
Author(s):
1. Layth Jasim Mohammed: Department of Microbiology, Faculty of Medicine, University of Babylon,Hilla City, Babylon Governorate,Iraq
2. Isaac Karimi: Department of Basic Sciences, College of Pharmacy, Al-Zahraa University for Women,,Iraq
3. Jasim Mohammed Abdulhussein: Department of Chemistry, Faculty of Medicine, University of Babylon,Hilla City, Babylon Governorate,Iraq
4. Ahmed M Sayed: Department of Pharmacognosy, Faculty of Pharmacy, Nahda University,Beni-Suef,Egypt
5. Zuhair Mohammed Ali Jeddoa: Department of Basic Sciences, College of Pharmacy, Al-Zahraa University for Women,,Iraq
6. Sabrean F Jawad: Department of Pharmacy, Al-Mustaqbal University College,Hillah, Babylon,Iraq
7. Mazin AA Najm: Department of Pharmaceutical Chemistry, College of Pharmacy, Al-Ayen University,Thi-Qar,Iraq
8. Majid S. Jabir: Department of Applied Sciences, University of Technology, Baghdad 10066, Iraq.
9. Benine Chaima: Department of Cellular and Molecular Biology, Faculty of Life and Natural Science, University of El Oued,,Algeria
Abstract:
Considering the current global pandemic and the urgent need to introduce novel drug candidates against severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), we reported at least four antipyretic recipes of Kurdish ethnomedicine which can be translated to functional antiviral formulations in orthodox medicine (Mohammed et al., 2020). Our current demanding computational work places much emphasis upon the implications of oleanolic acid and its analogues as a cluster of binder candidates of the main protease (Mpro) of SARS-CoV-2 which having a pivotal role in the pathogenesis of coronavirus disease 2019 (COVID-19). Through molecular docking and simulation studies, we found oleanolic acid (-12.6 Kcal/mol) and its two analogues (OA11; ligand I (-14.2 Kcal/mol)) and (OA31; ligand II (-14.0 Kcal/mol)) bound with Mpro (PDB: 6Y84) more reliable and trustful than saquinavir (-8.1 Kcal/mol) as a canonical drug. Salaspermic acid, (3b)-3-{[(2E)-3-phenylprop-2-enoyl]oxy}olean-12-en-28-oic acid, OA37 and OA40 interacted with catalytic dyad and major amino acid residues of active sites of Mpro and these toxic compounds should be considered in future anti-protease drug design. Overall, the current study seized the attention of experimentalists to the new set of antiprotease pentacyclic triterpenoids that should to be assayed against SARS-CoV-2 at in vitro or in clinical settings of COVID-19.
Page(s): 1039-1060
Published: Journal: Pakistan Journal of Pharmaceutical Sciences, Volume: 38, Issue: 3, Year: 2025
Keywords:
COVID19 , Covid19 , computational biology , acid toxicity , Mpro , oleanolic , Main Protease
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