Muhammad Hassan1, Atif Amin Baig2, Syed Awais Attique3, Shafqat Abbas4, Fizza Khan5, Sara Zahid5, Qurat Ul Ain6, Muhammad Usman7, Nordin Bin Simbak1, Mohammad Amjad Kamal8,9, Hanani Ahmad Yusof10. 1. Faculty of Medicine, Universiti Sultan Zainal Abidin (UniSZA), Jalan Sultan Mahmud, 20400, Kuala Terengganu, Terengganu Darul Iman, Malaysia. 2. Faculty of Medicine, Universiti Sultan Zainal Abidin (UniSZA), Jalan Sultan Mahmud, 20400, Kuala Terengganu, Terengganu Darul Iman, Malaysia. atifamin@unisza.edu.my. 3. Research Centre for Modelling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad, H-12, Pakistan. 4. School of Environmental Engineering, Suzhou University of Science and Technology, Suzhou New District, 215009, China. 5. Centre of Agricultural Biochemistry and Biotechnology (CABB), University of Agriculture, Faisalabad, 38000, Pakistan. 6. Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, 53700, Pakistan. 7. Department of Computer Science, University of Agriculture, Faisalabad, 38000, Pakistan. 8. King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Saudi Arabia. 9. Enzymoics, Novel Global Community Educational Foundation, 7 Peterlee Place, Hebersham, NSW, 2770, Australia. 10. Kulliyyah of Allied Health Sciences, International Islamic University Malaysia (IIUM), 25200, Kuantan, Pahang, Malaysia.
Abstract
PURPOSE: To predict potential inhibitors of alpha-enolase to reduce plasminogen binding of Streptococcus pneumoniae (S. pneumoniae) that may lead as an orally active drug. S. pneumoniae remains dominant in causing invasive diseases. Fibrinolytic pathway is a critical factor of S. pneumoniae to invade and progression of disease in the host body. Besides the low mass on the cell surface, alpha-enolase possesses significant plasminogen binding among all exposed proteins. METHODS: In-silico based drug designing approach was implemented for evaluating potential inhibitors against alpha-enolase based on their binding affinities, energy score and pharmacokinetics. Lipinski's rule of five (LRo5) and Egan's (Brain Or IntestinaL EstimateD) BOILED-Egg methods were executed to predict the best ligand for biological systems. RESULTS: Molecular docking analysis revealed, Sodium (1,5-dihydroxy-2-oxopyrrolidin-3-yl)-hydroxy-dioxidophosphanium (SF-2312) as a promising inhibitor that fabricates finest attractive charges and conventional hydrogen bonds with S. pneumoniae alpha-enolase. Moreover, the pharmacokinetics of SF-2312 predict it as a therapeutic inhibitor for clinical trials. Like SF-2312, phosphono-acetohydroxamate (PhAH) also constructed adequate interactions at the active site of alpha-enolase, but it predicted less favourable than SF-2312 based on binding affinity. CONCLUSION: Briefly, SF-2312 and PhAH ligands could inhibit the role of alpha-enolase to restrain plasminogen binding, invasion and progression of S. pneumoniae. As per our investigation and analysis, SF-2312 is the most potent naturally existing inhibitor of S. pneumoniae alpha-enolase in current time.
PURPOSE: To predict potential inhibitors of alpha-enolase to reduce plasminogen binding of Streptococcus pneumoniae (S. pneumoniae) that may lead as an orally active drug. S. pneumoniae remains dominant in causing invasive diseases. Fibrinolytic pathway is a critical factor of S. pneumoniae to invade and progression of disease in the host body. Besides the low mass on the cell surface, alpha-enolase possesses significant plasminogen binding among all exposed proteins. METHODS: In-silico based drug designing approach was implemented for evaluating potential inhibitors against alpha-enolase based on their binding affinities, energy score and pharmacokinetics. Lipinski's rule of five (LRo5) and Egan's (Brain Or IntestinaL EstimateD) BOILED-Egg methods were executed to predict the best ligand for biological systems. RESULTS: Molecular docking analysis revealed, Sodium (1,5-dihydroxy-2-oxopyrrolidin-3-yl)-hydroxy-dioxidophosphanium (SF-2312) as a promising inhibitor that fabricates finest attractive charges and conventional hydrogen bonds with S. pneumoniae alpha-enolase. Moreover, the pharmacokinetics of SF-2312 predict it as a therapeutic inhibitor for clinical trials. Like SF-2312, phosphono-acetohydroxamate (PhAH) also constructed adequate interactions at the active site of alpha-enolase, but it predicted less favourable than SF-2312 based on binding affinity. CONCLUSION: Briefly, SF-2312 and PhAH ligands could inhibit the role of alpha-enolase to restrain plasminogen binding, invasion and progression of S. pneumoniae. As per our investigation and analysis, SF-2312 is the most potent naturally existing inhibitor of S. pneumoniae alpha-enolase in current time.
Authors: Robert E Black; Simon Cousens; Hope L Johnson; Joy E Lawn; Igor Rudan; Diego G Bassani; Prabhat Jha; Harry Campbell; Christa Fischer Walker; Richard Cibulskis; Thomas Eisele; Li Liu; Colin Mathers Journal: Lancet Date: 2010-05-11 Impact factor: 79.321
Authors: Jiri Petrak; Robert Ivanek; Ondrej Toman; Radek Cmejla; Jana Cmejlova; Daniel Vyoral; Jan Zivny; Christopher D Vulpe Journal: Proteomics Date: 2008-05 Impact factor: 3.984
Authors: Alistair MacDougall; Vladimir Volynkin; Rabie Saidi; Diego Poggioli; Hermann Zellner; Emma Hatton-Ellis; Vishal Joshi; Claire O'Donovan; Sandra Orchard; Andrea H Auchincloss; Delphine Baratin; Jerven Bolleman; Elisabeth Coudert; Edouard de Castro; Chantal Hulo; Patrick Masson; Ivo Pedruzzi; Catherine Rivoire; Cecilia Arighi; Qinghua Wang; Chuming Chen; Hongzhan Huang; John Garavelli; C R Vinayaka; Lai-Su Yeh; Darren A Natale; Kati Laiho; Maria-Jesus Martin; Alexandre Renaux; Klemens Pichler Journal: Bioinformatics Date: 2020-11-01 Impact factor: 6.937