IDENTIFICATION OF PHYTOCOMPOUNDS FROM ARGEMONE MEXICANA AS INHIBITORS OF EPSTEIN-BARR NUCLEAR ANTIGEN TO COMBAT INFECTIOUS MONONUCLEOSIS
Keywords:Infectious mononucleosis, Argemone Mexicana, EBNA-1 and EBNA-2 antigen
Objectives: Mono or infectious mononucleosis (IM) is often referred to as the kissing illness. Epstein-Barr virus (EBV), which causes mono, is spread by saliva. Kissing, sharing a drink, or eating utensils with a person who has mononucleosis can transmit the disease to healthy individuals. This study investigates several bioactive compounds derived from plants to forecast how effective plant-based ligands will be at preventing IM.
Methods: The purpose of the current study was to use computational techniques to assess the effectiveness of several phytochemicals against the EBV. The virtual screening tool PyRx was used to systematically perform molecular docking. The top 6 phytocompounds from Argemone mexicana were chosen among them to test their compatibility with the EBV nuclear antigen. Using ADMET filters, the ligands’ pharmacological evaluation was performed.
Results: The phytocompounds Coptisine, Sanguinarine, and Dihydrosanguinarine from the plant A. mexicana were discovered to be the most potent antagonistic for the proteins EBV Nuclear Antigen 1 and EBV nuclear antigen 2.
Conclusion: All of these bioactive chemicals could be considered of as deserving candidates for the suppression of IM due to their strong affinity for the protein. Among the top ligand, the phytoconstituent Coptisine demonstrated better binding with both targets.
Bar-Or A, Pender MP, Khanna R, Steinman L, Hartung HP, Maniar T, et al. Epstein-Barr virus in multiple sclerosis: Theory and emerging immunotherapies. Trends Mol Med 2020;26:296-310.
Farrell PJ. Epstein-Barr virus and cancer. Annu Rev Pathol 2019;14: 29-53.
Bjornevik K, Cortese M, Healy BC, Kuhle J, Mina MJ, Leng Y, et al. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 2022;375:296-301.
Thorley-Lawson DA. Epstein-Barr virus: Exploiting the immune system. Nat Rev Immunol 2001;1:75-82.
Shannon-Lowe C, Rickinson AB, Bell AI. Epstein-Barr virus-associated lymphomas. Philos Trans R Soc Lond B Biol Sci 2017;372:20160271.
Sivachandran N, Wang X, Frappier L. Functions of the Epstein-Barr virus EBNA1 protein in viral reactivation and lytic infection. J Virol 2012;86:6146-58.
Mansouri S, Pan Q, Blencowe BJ, Claycomb JM, Frappier L. Epstein- Barr virus EBNA1 protein regulates viral latency through effects on let-7 microRNA and dicer. J Virol 2014;88:11166-77.
Schulz TF, Cordes S. Is the Epstein-Barr virus EBNA-1 protein an oncogen? Proc Natl Acad Sci U S A 2009;106:2091-2.
Gianti E, Messick TE, Lieberman PM, Zauhar RJ. Computational analysis of EBNA1 “druggability” suggests novel insights for Epstein- Barr virus inhibitor design. J Comput Aided Mol Des 2016;30:285-303.
Henkel T, Ling PD, Hayward SD, Peterson MG. Mediation of Epstein- Barr virus EBNA2 transactivation by recombination signal-binding protein J kappa. Science 1994;265:92-5.
Lucchesi W, Brady G, Dittrich-Breiholz O, Kracht M, Russ R, Farrell PJ. Differential gene regulation by Epstein-Barr virus Type 1 and Type 2 EBNA2. J Virol 2008;82:7456-66.
Mukhtar M, Arshad M, Ahmad M, Pomerantz RJ, Wigdahl B, Parveen Z. Antiviral potentials of medicinal plants. Virus Res 2008;131:111-20.
Brahmachari G, Gorai D, Roy R. Argemone mexicana: Chemical and pharmacological aspects. Rev Bras Farmacogn 2013;23:559-67.
Bhattacharjee I, Chatterjee SK, Chatterjee S, Chandra G. Antibacterial potentiality of Argemone mexicana solvent extracts against some pathogenic Bacteria. Mem Inst Oswaldo Cruz 2006;101:645-8.
Priya CL, Rao KV. Ethanobotanical and current ethanopharmacological aspects of Argemone mexicana Linn: An overview. Int J Pharm Sci Res 2012;3:2143.
Mohanraj K, Karthikeyan BS, Vivek-Ananth RP, Chand RP, Aparna SR, Mangalapandi P, et al. IMPPAT: A curated database of Indian medicinal plants, phytochemistry and therapeutics. Sci Rep 2018;8:4329.
Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem in 2021: New data content and improved web interfaces. Nucleic Acids Res 2021;49:D1388-95.
Burley SK, Berman HM, Kleywegt GJ, Markley JL, Nakamura H, Velankar S. Protein data bank (PDB): The single global macromolecular structure archive. Methods Mol Biol 2017;1607:627-41.
Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al. SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Res 2018;46:W296-303.
Jejurikar BL, Rohane SH. Drug designing in discovery studio. Asian J Res Chem 2021;14:135-8.
Zhou AQ, O’Hern CS, Regan L. Revisiting the ramachandran plot from a new angle. Protein Sci 2011;20:1166-71.
Daina A, Michielin O, Zoete V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017;7:42717.
Yang H, Lou C, Sun L, Li J, Cai Y, Wang Z, et al. Admetsar 2.0: Web-service for prediction and optimization of chemical ADMET properties. Bioinformatics 2019;35:1067-9.
Kondapuram SK, Sarvagalla S, Coumar MS. Docking-based virtual screening using PyRx tool: Autophagy target Vps34 as a case study. In: Molecular Docking for Computer-Aided Drug Design. Amsterdam: Elsevier Inc.; 2021. p. 463-77.
How to Cite
Copyright (c) 2023 Mohammed Shafiq K, Rohit Harish, SAMEER SHARMA
This work is licensed under a Creative Commons Attribution 4.0 International License.