Author/Authors :
Hassan, Muhammad Faculty of Medicine - Universiti Sultan Zainal Abidin (UniSZA) - Jalan Sultan Mahmud - Terengganu Darul Iman, Malaysia , Amin Baig, Atif Faculty of Medicine - Universiti Sultan Zainal Abidin (UniSZA) - Jalan Sultan Mahmud - Terengganu Darul Iman, Malaysia , Attique, Awais Research Centre for Modelling and Simulation (RCMS) - National University of Sciences and Technology (NUST), Pakistan , Abbas, Shafqat School of Environmental Engineering - Suzhou University of Science and Technology, China , Khan, Fizza Centre of Agricultural Biochemistry and Biotechnology (CABB) - University of Agriculture, Pakistan , Zahid, Sara Centre of Agricultural Biochemistry and Biotechnology (CABB) - University of Agriculture, Pakistan , Ul Ain, Qurat Centre for Applied Molecular Biology (CAMB) - University of the Punjab, Pakistan , Usman, Muhammad Department of Computer Science - University of Agriculture, Pakistan , Simbak, Nordin Bin Faculty of Medicine - Universiti Sultan Zainal Abidin (UniSZA) - Jalan Sultan Mahmud - Terengganu Darul Iman, Malaysia , Kamal, Mohammad Amjad King Fahd Medical Research Center - King Abdulaziz University, Saudi Arabia , Ahmad Yusof, Hanani Kulliyyah of Allied Health Sciences - International Islamic University Malaysia (IIUM), Malaysia
Abstract :
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 (SF2312) 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 predictedless 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, invasionand progression of S. pneumoniae. As per our investigation and analysis, SF-2312 is the most potent naturally existing inhibitorof S. pneumoniae alpha-enolase in current time
Keywords :
SF-2312 , Molecular docking , NETs , Enolase ligands , PhAH
