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

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.

Graphical abstract

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Data availability

All data produced during the current study are available from the corresponding author on reasonable request.

Abbreviations

5TX:

((3 s,5 s)-1,5-Dihydroxy-3-Methyl-2-Oxopyrrolidin-3-Yl)phosphonic acid

6BM:

[(3 s)-1-Hydroxy-2-Oxopiperidin-3-Yl]phosphonic acid

BOILED:

Brain Or IntestinaL EstimateD

FSG:

(1 s)-1-Fluoro-2-(Hydroxyamino)-2-Oxoethyl]phosphonic acid

IPD:

Invasive pneumococcal disease

KVM:

[(3S)-1-Hydroxy-2,5-Dioxopyrrolidin-3-Yl]phosphonic acid

LRo5:

Lipinski’s rule of five

NETs:

Neutrophil Extracellular Traps

PhAH:

Phosphono-acetohydroxamate

PLG:

Plasminogen

SF-2312:

Sodium (1,5-dihydroxy-2-oxopyrrolidin-3-yl)-hydroxy-dioxidophosphanium

S. pneumoniae :

Streptococcus pneumoniae

TPSA:

Topological polar surface area

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Acknowledgements

The research is supported by FRGS/1 /2017/SKK06iUNISZA/02/1 under Kementerian Pendidikan Malaysia (KPM) and Universiti Sultan Zainal Abidin.

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Contributions

Conceptualization: Muhammad Hassan and Atif Amin Baig; Methodology: Muhammad Hassan, Atif Amin Baig, Nordin Bin Simbak and Mohammad Amjad Kamal; Software analysis: Muhammad Hassan, Syed Awais Attique, Shafqat Abbas and Muhammad Usman; Validation: Fizza Khan, Sara Zahid, Qurat Ul Ain; Writing – original draft: Muhammad Hassan, Sara Zahid, Qurat Ul Ain; Writing – review & editing: Atif Amin Baig and Hanani Ahmad Yusof.

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Correspondence to Atif Amin Baig.

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Hassan, M., Baig, A.A., Attique, S.A. et al. Molecular docking of alpha-enolase to elucidate the promising candidates against Streptococcus pneumoniae infection. DARU J Pharm Sci (2021). https://doi.org/10.1007/s40199-020-00384-3

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Keywords

  • SF-2312
  • PhAH
  • Enolase ligands
  • NETs
  • Molecular docking