Binding affinities and molecular dynamics simulations of selected approved drugs and Mucuna pruriens phytoconstituents with Escherichia coli Shiga toxin
1 Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Chukwuemeka Odumegwu Ojukwu University Igbariam, Igbariam Anambra State, Nigeria.
2 Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Chukwuemeka Odumegwu Ojukwu University Igbariam, Igbariam Anambra State, Nigeria.
3 Department of Pharmacognosy and Traditional Medicine, Faculty of Pharmaceutical Sciences, Chukwuemeka Odumegwu Ojukwu University Igbariam, Igbariam Anambra State, Nigeria.
4 Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University Awka, Anambra State, Nigeria.
Research Article
GSC Biological and Pharmaceutical Sciences, 2025, 30(02), 029–035.
Article DOI: 10.30574/gscbps.2025.30.2.0038
Publication history:
Received on 18 December 2024; revised on 01 February 2025; accepted on 04 February 2025
Abstract:
Shiga toxin (Stx)–producing Escherichia coli (STEC), also known as “verocytotoxin- producing E. coli” is a major food and waterborne pathogen of zoonotic origin. STEC infection is involved in several life-threatening disease conditions that includes diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome. We determined the binding affinities of selected approved drugs and Mucuna pruriens phytoconstituents to shiga toxin and ricin receptors (a toxin similar in structure to shiga toxin) by molecular docking simulations. The 3D crystal structures of Stx1, Stx2 and ricin receptor were obtained from the protein data bank. The receptors were prepared using PyMol 1.1eval, Chimera 1.10.1 and AutoDock tools vs 1.5.6. The 3D structures of selected approved drugs and Mucuna pruriens phytoconstituents were obtained from ZINC and PubChem databases. They were prepared for molecular docking simulations using AutoDock tools vs 1.5.6. Docking protocols were validated by reproducing the PDB crystal structures in silico. Molecular docking simulations were executed with a virtual screening script using AutoDockVina 1.1.2 on a Linux platform. Molecular dynamics simulations of two front runner compounds with the reference ligand and protein were done in 1500 ps. Morphine, Butorphanol and riboflavin (phytoconstituent of Mucuna pruriens) had binding affinities of -6.6±0.0,-6.4±0.1 and -6.2±0.1 kcal/mol respectively as while the reference ligand, 3-(pyridine-1-ium-1-yl)propane-1-sulfonate had binding affinity of -4.5±0.0kcal/mol. Higher stability were demonstrated by morphine and butorphanol in the molecular dynamics simulations. Morphine, butorphanol and riboflavin are predicted as possible shiga toxin antidotes.
Keywords:
Shiga toxin; Molecular docking; Molecular dynamics; Approved drugs; Escherichia coli; Mucuna pruriens
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