STM Journals Peer-reviewed research from Consortium e-Learning Network

International Journal of Molecular Biotechnological Research Original Research

Exploring Potential Phytochemicals for Myasthenia Gravis Treatment: A Molecular Docking and ADME Analysis Approach

  1. Neha Subhash Nilawad Departmentof Bioinformatics, Institute of Bioscience and Technology, MGM University, Chhatrapati Sambhaji Nagar

Abstract

Objective: Muscle feebleness and exhaustion derived from a disruption in neuromuscular transference are hallmarks of the crippling autoimmune disease myasthenia gravis (MG). The drawbacks of the current MG therapy options are frequently partial efficacy and adverse effects. To investigate the potential of phytochemicals in MG control, in this work we integrated molecular docking with ADME (absorption, distribution, metabolism, and excretion) analysis using a computer method. We identified molecules exhibiting favorable interactions with key molecular targets implicated in MG pathophysiology, such as muscle-specific kinase (MuSK), nicotinic acetylcholine receptors (nAChRs), and acetylcholinesterase (AChE). Explore the natural substances called phytochemicals that are derived from plants and may have therapeutic uses in treating a variety of ailments, including autoimmune disorders. This has become more and more popular in the past few years.

Methods: Theoretical Methodology: This study aims to explore the potential of phytochemicals from the Cassia fistula medicinal plant for the treatment of Myasthenia gravis (MG) through a multi-step computational approach. Firstly, the top five phytochemicals from Cassia fistula will be selected based on a literature review and computational screening. These compounds will then undergo molecular docking onto the active site of the muscle-specific kinase (MuSK) protein (PDB ID: 1LUF) using PyRx software to predict their binding affinities and interactions. Following this, ADME (absorption, distribution, metabolism, and excretion) analysis will be conducted to evaluate the pharmacokinetic properties of the docked compounds, including bioavailability and toxicity. To identify possible lead compounds for additional experimental validation, Biovia software will be used to visualize protein-ligand interactions. This integrated approach holds promise for the discovery of novel phytochemical-based therapeutics for MG treatment.

Result: Molecular docking investigations indicated that Rhein, chrysophanic acid, aromadendrin, aloe emodin, and anthraquinone were in the ligands with the lowest binding affinities to the targeted proteins.

Conclusion: In conclusion, we have effectively discovered phytochemicals with promise for treating Myasthenia gravis (MG) by our molecular docking and ADME analysis technique utilizing Biovia and PyRx. Using computational screening, we found phytochemicals with good pharmacokinetic characteristics and a substantial binding affinity to MG-related target proteins. These results demonstrate the possibility of using natural substances as MG treatment alternatives. To determine these compounds’ safety and efficacy and to prepare the way for the creation of novel MG therapies based on phytochemicals, more experimental validation of these compounds is necessary.

Keywords

References (23)

  1. Thanvi BR, Lo TCN. Update on myasthenia gravis. Postgraduate Medical Journal. 2004;80(950):690-700. doi:10.1136/pgmj.2004.018903
  2. Eldaabossi S, Alrashdan M, Aljanobi G, Warsha N, Abo Elhassan S, Mahdi W, et al. A rare association: Obesity hypoventilation syndrome with myasthenia gravis and systemic lupus erythematosus, case report. Respiratory Medicine Case Reports. 2023;44:101848. doi:10.1016/j.rmcr.2023.101848
  3. Cao M, Koneczny I, Vincent A. Myasthenia Gravis With Antibodies Against Muscle Specific Kinase: An Update on Clinical Features, Pathophysiology and Treatment. Frontiers in Molecular Neuroscience. 2020;13. doi:10.3389/fnmol.2020.00159
  4. Jayam Trouth A, Dabi A, Solieman N, Kurukumbi M, Kalyanam J. Myasthenia Gravis: A Review. Autoimmune Diseases. 2012;2012:1-10. doi:10.1155/2012/874680
  5. Marsteller HB. The First American Case of Myasthenia Gravis. Archives of Neurology. 1988;45(2):185-187. doi:10.1001/archneur.1988.00520260073024
  6. Somnier FE. Myasthenia gravis-occurrence, failure in neuromuscular transmission, clinical implementation of anti-AChR antibodies, and therapeutic progress. Dan Med Bull. 1996;43(1):1–10.
  7. Evoli A. Acquired myasthenia gravis in childhood. Current Opinion in Neurology. 2010;23(5):536-540. doi:10.1097/wco.0b013e32833c32af
  8. Evoli A, Bianchi MR, Riso R, Minicuci GM, Batocchi AP, Servidei S, et al. Response to Therapy in Myasthenia Gravis with Anti‐MuSK Antibodies. Annals of the New York Academy of Sciences. 2008;1132(1):76-83. doi:10.1196/annals.1405.012
  9. Jaretzki A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, et al. Myasthenia gravis: recommendations for clinical research standards. Neurol. 2000;55(1):16–23. doi:10.1212/WNL.55.1.1.
  10. Skeie GO, Apostolski S, Evoli A, Gilhus NE, Illa I, Harms L, et al. Guidelines for treatment of autoimmune neuromuscular transmission disorders. European Journal of Neurology. 2010;17(7):893-902. doi:10.1111/j.1468-1331.2010.03019.x
  11. Elovaara I, Apostolski S, Van Doorn P, Gilhus NE, Hietaharju A, Honkaniemi J, et al. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases. European Journal of Neurology. 2008;15(9):893-908. doi:10.1111/j.1468-1331.2008.02246.x
  12. Leite MI, Waters P, Vincent A. Diagnostic use of autoantibodies in myasthenia gravis. Autoimmunity. 2010;43(5-6):371-379. doi:10.3109/08916930903541208
  13. Matsumoto Y, Matsuo H, Sakuma H, Park IK, Tsukada Y, Kohyama K, et al. CDR3 Spectratyping Analysis of the TCR Repertoire in Myasthenia Gravis. The Journal of Immunology. 2006;176(8):5100-5107. doi:10.4049/jimmunol.176.8.5100
  14. Mohanraj K, Karthikeyan BS, Vivek-Ananth RP, Chand RPB, Aparna SR, Mangalapandi P, et al. IMPPAT: A curated database of Indian Medicinal Plants, Phytochemistry And Therapeutics. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-22631-z
  15. Saldívar-González FI, Huerta-García CS, Medina-Franco JL. Chemoinformatics-based enumeration of chemical libraries: a tutorial. J Cheminform. 2020;12(1):64. doi:10.1186/s13321-020-00466
  16. Shann-Ching Chen, Tsuhan Chen. Retrieval of 3D protein structures. Proceedings. International Conference on Image Processing. 1:933-936. doi:10.1109/icip.2002.1039126
  17. Schwede T. SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Research. 2003;31(13):3381-3385. doi:10.1093/nar/gkg520
  18. Adrees S, Imtiaz A, Yaseen A, Irfan Fareed M, Anwar W, Ashraf A, et al. In-silico analysis of potential anticancer drug for NEK7 and PPP1CA proteins overexpressed in pancreatic ductal adenocarcinoma. Journal of Biomolecular Structure and Dynamics. 2024;43(13):6581-6597. doi:10.1080/07391102.2024.2318484
  19. Ahmad I, Khan H, Serdaroğlu G. Physicochemical properties, drug likeness, ADMET, DFT studies, and in vitro antioxidant activity of oxindole derivatives. Computational Biology and Chemistry. 2023;104:107861. doi:10.1016/j.compbiolchem.2023.107861
  20. Morris GM, Lim-Wilby M. Molecular Docking. Methods in Molecular Biology. 2008:365-382. doi:10.1007/978-1-59745-177-2_19
  21. Dallakyan S, Olson AJ. Small-Molecule Library Screening by Docking with PyRx. Methods in Molecular Biology. 2014:243-250. doi:10.1007/978-1-4939-2269-7_19
  22. Shaweta S, Akhil S, Utsav G. Molecular Docking studies on the Anti-fungal activity of Allium sativum (Garlic) against Mucormycosis (black fungus) by BIOVIA discovery studio visualizer 21.1.0.0. Annals of Antivirals and Antiretrovirals. 2021:028-032. doi:10.17352/aaa.000013
  23. Morris AL, MacArthur MW, Hutchinson EG, Thornton JM. Stereochemical quality of protein structure coordinates. Proteins: Structure, Function, and Bioinformatics. 1992;12(4):345-364. doi:10.1002/prot.340120407