Molecular docking of alpha-enolase to elucidate the promising candidates against Streptococcus pneumoniae infection

• Published in: Daru Vol. 29; no. 1; pp. 73 - 84
• Main Authors: Hassan, Muhammad, Baig, Atif Amin, Attique, Syed Awais, Abbas, Shafqat, Khan, Fizza, Zahid, Sara, Ain, Qurat Ul, Usman, Muhammad, Simbak, Nordin Bin, Kamal, Mohammad Amjad, Yusof, Hanani Ahmad
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2021; BioMed Central Ltd; Springer Nature B.V
• Subjects: Administration, Oral; Analysis; Bacterial pneumonia; Biomedical and Life Sciences; Biomedicine; Development and progression; Health aspects; Hydrogen; Hydroxamic Acids - chemistry; Hydroxamic Acids - pharmacokinetics; Medicinal Chemistry; Molecular Docking Simulation; Organophosphonates - chemistry; Organophosphonates - pharmacokinetics; Pharmaceutical Sciences/Technology; Pharmacokinetics; Pharmacology/Toxicology; Phosphonoacetic Acid - analogs & derivatives; Phosphonoacetic Acid - chemistry; Phosphonoacetic Acid - pharmacokinetics; Phosphopyruvate Hydratase - antagonists & inhibitors; Phosphopyruvate Hydratase - chemistry; Phosphopyruvate Hydratase - metabolism; Pneumococcal Infections - drug therapy; Pneumonia; Protein binding; Proteins; Pyrrolidinones - chemistry; Pyrrolidinones - pharmacokinetics; Research Article; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - enzymology; Enolase ligands; NETs; PhAH; SF-2312; Molecular docking
• ISSN: 2008-2231; 1560-8115; 2008-2231
• DOI: 10.1007/s40199-020-00384-3

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. Graphical abstract