Volume 15, Issue 36, July - December, 2021

Molecular docking and dynamics simulation of L-hyoscyamine, eupatorium and alkaloid L27 as potential inhibitors against 3CLpro of SARS-CoV-2

Mandal M¹, Mandal S^2♦

¹Department of Physiology, MGM Medical College, Kishanganj-855107, India
²Department of Zoology, Laboratory of Microbiology and Experimental Medicine, University of Gour Banga, Malda-732103, India

^♦Corresponding author
Prof. Shyamapada Mandal, Laboratory of Microbiology and Experimental Medicine, Department of Zoology, University of Gour Banga, Malda-732103, India;

ABSTRACT

Background & objectives: The COVID-19 pandemic, caused with the infection of SARS-CoV-2, is long lasting, and there is no specific treatment for the disease. The current study authenticates, using bioinformatic approaches, the inhibition of SARS-CoV-2 3CLpro with three bioactive phytochemicals alkaloid L27, eupatorium and L-hyoscyamine from Lycopodium clavatum, Eupatorium perfoliatum and Atropa belladonna, respectively. Methods: Molecular docking, ADMET, drug‐likeness analysis, molecular dynamics (MD) simulation, and free energy calculation were applied to 3CLpro interaction with alkaloid L27, eupatorium and L-hyoscyamine, for the determination of pharmacological efficacy, safety evaluation, to assess the dynamics and energetics of these complexes. Results: Molecular docking demonstrated binding energy ≤ -6.5 kcal/mol for the phytochemicals used as ligands. No violation of Lipinski’s RO5, favourable ADMET properties and bioavailability scores (0.55) signify the suitability of drug-likeness for the selected ligands. Molecular dynamic simulation revealed the root mean square (RMS) deviation of ~ 0.12 nm about the protein backbone, and RMS fluctuations < 0.2 nm about the ligand-heavy atoms, indicating the stability of protein-ligand complex structures throughout the simulation course. Interpretation & conclusions: The key amino acid players in protein-ligand interactions were Lys5, Met6, Ala7 and Val125 through H-bond and hydrophobic bond formation. Though net binding free energy of 3CLPro with eupatorium (-121.36 kJ/mol) was more favorable than lycopodium (-114.17 kJ/mol) and L-hyoscyamine (-78.96 kJ/mol), all the ligands were found effective to inhibit the 3CLpro of SARSCoV-2. Thus, the compounds alkaloid L27 from Lycopodium, eupatorium, and L-hyoscyamine might be useful in the management of COVID-19 associated symptoms

Keywords: Atropa belladonna, Eupatorium perfoliatum, Lycopodium clavatum, molecular docking, molecular dynamics simulation, SARS-CoV-2 3CLpro

Drug Discovery, 2021, 15(36), 181-201

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