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Year : 2022  |  Volume : 18  |  Issue : 79  |  Page : 773-782

Lapachol and (α/β)-lapachone as inhibitors of SARS-CoV-2 Main Protease (Mpro) and hACE-2: ADME properties, docking and dynamic simulation approaches

1 Department of Biology, University of Hail, College of Science, P.O. Box 2440, Ha'il 2440, Saudi Arabia; Laboratory of Genetics, Biodiversity and Valorisation of Bioressources, High Institute of Biotechnology--University of Monastir, Monastir 5000, Tunisia
2 Division of Computer Aided Drug Design, Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, India
3 Department of Biology, University of Hail, College of Science, P.O. Box 2440, Ha'il 2440, Saudi Arabia; Laboratory of Bioressources: Integrative Biology and Recovery, High Institute of Biotechnology--University of Monastir, Monastir 5000, Tunisia
4 Department of Public Health, College of Public Health and Health Informatics, Ha'il, Saudi Arabia
5 Department of Biology, University of Hail, College of Science, P.O. Box 2440, Ha'il 2440, Saudi Arabia
6 Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, University of Ha'il, Ha'il, Saudi Arabia
7 Department of Pharmaceutics, College of pharmacy, University of Hail, Kingdom of Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, University of Khartoum, Sudan
8 Laboratoire de Chimie Appliquée: Hétérocycles, Corps Gras et Polymères, Faculté des Sciences de Sfax, Université de Sfax. B. P, 802. 3000 Sfax, Tunisie
9 Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, Salerno 84084, Italy
10 Department of Chemistry, Faculty of Science, Al--Azhar University, Assiut 71524, Egypt
11 Department of Chemistry, College of Science, Qassim University, Buraidah 51452, Saudi Arabia; University of Monastir, Faculty of Science of Monastir, Avenue of the Environment, 5019 Monastir, Tunisia
12 Department of Chemistry, Faculty of Science and Arts of Baljurashi, Albaha University, Saudi Arabia; Faculty of Science of Sfax, Department of Chemistry, University of Sfax, B.P. 1171, 3000 Sfax, Tunisia

Correspondence Address:
Mejdi Snoussi
Department of Biology, University of Hail, College of Science, P.O. Box 2440, Ha'il 2440

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/pm.pm_251_22

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Background: Tabebuia impetiginosa is an important medicinal plant rich in lapachol, α-lapachone, and β-lapachone known to possess several biological activities. Objective: In this study, we investigated the drug potential of lapachol, α-lapachone, and β-lapachone using molecular docking, molecular dynamic (MD), and drug-likeness properties. Materials and Methods: The computational study was performed using SwissADME software for the determination of the pharmacokinetic properties of the tested compounds. AutoDock Vina and Genetic Optimization for Ligand Docking (GOLD) were used for the docking analysis, and MD simulations were run using Schrodinger's Desmond Simulation. Results: The three compounds lapachol, α-lapachone, and β-lapachone binds to cysteine (Cys)-histidine (His) catalytic dyad (Cys145 and His41) along with the other residues with, respectively, the following docking score 48.69, 47.06, and 47.79. Against viral entry receptor, human angiotensin-converting enzyme 2 (hACE-2), α-lapachone exhibited the highest GOLD Fitness score complex (54.82) followed by lapachol (42.53) and β-lapachone and hACE-2 (38.74) generating several active sites in the target proteins. A 100 ns MDs simulation study revealed the stable conformation of bioactive compounds within the cavity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of hACE-2 protein and main protease (Mpro). From the dynamic study, it was observed that lapachol was tightly bound with catalytic dyad residue Cys145 of Mpro with more than 40% time of simulation, also post-simulation MM-GBSA binding free energy (ΔG Bind) revealed the highest energy score (−51.18 ± 5.14 kcal/mol) among the evaluated complex. Moreover, the absorption, distribution, metabolism, and excretion (ADME) properties demonstrated that the investigated compounds passed the pharmacokinetic and drug-likeness criteria without undesirable effects. Conclusion: The computational study highlighted that these compounds could be highly recommended and developed as part of an effective drug against the SARS-CoV-2 virus.

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