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

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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.

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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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Authors and Affiliations

  1. Faculty of Medicine, Universiti Sultan Zainal Abidin (UniSZA), Jalan Sultan Mahmud, 20400, Kuala Terengganu, Terengganu Darul Iman, Malaysia

    Muhammad Hassan, Atif Amin Baig & Nordin Bin Simbak

  2. Research Centre for Modelling and Simulation (RCMS), National University of Sciences and Technology (NUST), Islamabad, H-12, Pakistan

    Syed Awais Attique

  3. School of Environmental Engineering, Suzhou University of Science and Technology, Suzhou New District, 215009, China

    Shafqat Abbas

  4. Centre of Agricultural Biochemistry and Biotechnology (CABB), University of Agriculture, Faisalabad, 38000, Pakistan

    Fizza Khan & Sara Zahid

  5. Centre for Applied Molecular Biology (CAMB), University of the Punjab, Lahore, 53700, Pakistan

    Qurat Ul Ain

  6. Department of Computer Science, University of Agriculture, Faisalabad, 38000, Pakistan

    Muhammad Usman

  7. King Fahd Medical Research Center, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Saudi Arabia

    Mohammad Amjad Kamal

  8. Enzymoics, Novel Global Community Educational Foundation, 7 Peterlee Place, Hebersham, NSW, 2770, Australia

    Mohammad Amjad Kamal

  9. Kulliyyah of Allied Health Sciences, International Islamic University Malaysia (IIUM), 25200, Kuantan, Pahang, Malaysia

    Hanani Ahmad Yusof

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  1. Muhammad Hassan
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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 29, 73–84 (2021). https://doi.org/10.1007/s40199-020-00384-3

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