Repurposing the natural compounds as potential therapeutic agents for COVID-19 based on the molecular docking study of the main protease and the receptor-binding domain of spike protein
Vajiheh Eskandari
Journal of Molecular Modeling, doi:10.1007/s00894-022-05138-3
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) enters the cell by interacting with the human angiotensinconverting enzyme 2 (ACE2) receptor through the receptor-binding domain (RBD) of spike (S) protein. In the cell, the viral 3-chymotrypsin-like cysteine protease (3CLpro) enzyme is essential for its life cycle and controls coronavirus replication. Therefore, the S-RBD and 3CLpro are hot targets for drug discovery against SARS-CoV-2. This study was to identify repurposing drugs using in silico screening, docking, and molecular dynamics simulation. The study identified bentiamine, folic acid, benfotiamine, and vitamin B12 against the RBD of S protein and bentiamine, folic acid, fursultiamine, and riboflavin to 3CLpro. The strong and stable binding of these safe and cheap vitamins at the important residues (R403, K417, Y449, Y453, N501, and Y505) in the S-protein-ACE2 interface and 3CLpro binding site residues especially active site residues (His 41 and Cys 145), indicating that they could be valuable repurpose drugs for inhibiting SARS-CoV-2 entry into the host and replication.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s00894-022-05138-3.
Author contribution This manuscript has been done by myself, and there was no coauthor.
Declarations Ethics approval This study does not require ethics approval. Consent to participate This study does not require participant approval. Consent for publication This study does not require publication approval.
Competing interests The author declares no competing interests. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
Abraham, Gready, Optimization of parameters for molecular dynamics simulation using smooth particle-mesh Ewald in GROMACS 4.5, J Comput Chem
Bae, Kamynina, Farinola, Caudill, Stover et al., Provision of folic acid for reducing arsenic toxicity in arsenic-exposed children and adults, Cochrane Database Syst Rev
Ben-Eltriki, Guns, Calcitriol in combination therapy for prostate cancer: pharmacokinetic and pharmacodynamic interactions, J Cancer
Berendsen, Van Der Spoel, Van Drunen, GROMACS: a message-passing parallel molecular dynamics implementation, Comput Phys Commun
Berman, Westbrook, Feng, Gilliland, Bhat et al., The Protein Data Bank, Nucleic Acids Res
Bolton, Wang, Thiessen, Bryant, PubChem: integrated platform of small molecules and biological activities, Annual reports in computational chemistry
Chen, Yiu, Wong, Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL (pro)) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates, F1000Res
Chikhale, Gurav, Patil, Sinha, Prasad et al., SARS-CoV-2 host entry and replication inhibitors from Indian ginseng: an in-silico approach, J Biomol Struct Dyn
Corrêa, Barros, Fernandes, Sokovic, Bracht et al., A natural food ingredient based on ergosterol: optimization of the extraction from Agaricus blazei, evaluation of bioactive properties and incorporation in yogurts, Food Funct
Dallakyan, Olson, Small-molecule library screening by docking with PyRx, Methods Mol Biol
Fehr, Perlman, Coronaviruses: an overview of their replication and pathogenesis, Methods Mol Biol
Gahlawat, Kumar, Kumar, Sandhu, Singh et al., Structure-based virtual screening to discover potential lead molecules for the SARS-CoV-2 main protease, J Chem Inf Model
Hanwell, Curtis, Lonie, Vandermeersch, Zurek et al., Avogadro: an advanced semantic chemical editor, visualization, and analysis platform, J Cheminform
Heywood, Wood, Majeed, Tumorigenic and toxic effect of O, S-dibenzoyl thiamine hydrochloride in prolonged dietary administration to rats, Toxicol Lett
Khan, Zia, Ashraf, Uddin, Ul-Haq, Identification of chymotrypsin-like protease inhibitors of SARS-CoV-2 via integrated computational approach, J Biomol Struct Dyn
Laskowski, Swindells, LigPlot+: multiple ligandprotein interaction diagrams for drug discovery, J Chem Inf Model
Martoňák, Laio, Parrinello, Predicting crystal structures: the Parrinello-Rahman method revisited, Phys Rev Lett
Morris, Huey, Lindstrom, Sanner, Belew et al., AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, J Comput Chem
Naqvi, Fatima, Mohammad, Fatima, Singh et al., Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: structural genomics approach, Biochim Biophys Acta (BBA)-Mol Basis Dis
Ravichandran, Coyle, Klenow, Tang, Grubbs et al., Antibody signature induced by SARS-CoV-2 spike protein immunogens in rabbits, Sci Transl Med
Satake, Amano, Okamoto, Calcipotriol and betamethasone dipropionate synergistically enhances the balance between regulatory and proinflammatory T cells in a murine psoriasis model, Sci Rep
Schmid, Eichenberger, Choutko, Riniker, Winger et al., Testing of the GROMOS force-field versions: 54A7 and 54B7, Eur Biophys J
Schoeman, Fielding, Coronavirus envelope protein: current knowledge, Virol J
Schrödinger, None, PyMOL. The PyMOL Molecular Graphics System
Schüttelkopf, Van Aalten, PRODRG: a tool for high-throughput crystallography of protein-ligand complexes, Acta Crystallogr Sect D
Turner, XMGRACE, Version 5.1. 19
Unni, Aouti, Thiyagarajan, Padmanabhan, Identification of a repurposed drug as an inhibitor of spike protein of human coronavirus SARS-CoV-2 by computational methods, J Biosci
Visualizer, Version 4.5. Softw Vis Anal Protein Struct
Vogel, Dali-Youcef, Kaltenbach, Andres, Homocysteine, vitamin B12, folate and cognitive functions: a systematic and critical review of the literature, Int J Clin Pract
Wu, Zhao, Yu, Chen, Song, A new coronavirus associated with human respiratory disease in China, Nature
Yang, Wang, COVID-19: a new challenge for human beings, Cell Mol Immunol
Yoshida, Hishiyama, Igarashi, A novel method for determining total vitamin B1 in processed food enriched with dibenzoyl thiamine, J Jpn Soc Food Sci Technol
