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Screening cyclooxygenase-2 inhibitors from Allium sativum L. compounds: in silico approach

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Abstract

Inflammation is a natural protective response toward various simulators, including tissue damage or pathogens. The cyclooxygenase-2 (COX-2) is a very important protein in triggering pain and inflammation. Previous studies have claimed that Allium sativum offers a wide range of anti-inflammatory therapeutics for human consumption. Drug discovery is a complicated process, though in silico methods can make this procedure simpler and more cost-effective. At the current study, we performed the virtual screening of eight Allium sativum–derived compounds via molecular docking with COX-2 enzyme and confirmed the binding energy by docking score estimate followed by ADMET and drug-likeness investigation. The resulting highest-docking scored compound was exposed to molecular dynamics simulation (MDS) for evaluating stability of the docked enzyme-ligand complex and to gauge the oscillation and conformational alterations for the time of enzyme-ligand interaction. The factors of RMSD, RMSF, hydrogen bond interactions, and Rg after 100 ns of MDS proved the stability of alliin in the active site of COX-2 in comparison with celecoxib (CEL) as the control. Moreover, we investigated the binding affinity analysis of all compounds via MM/PBSA method. The results from this study suggest that alliin (a sulfuric compound) exhibits a higher binding affinity for the COX-2 enzyme compared to the other compounds and CEL. Alliin showed to be a possible anti-inflammatory therapeutic candidate for managing the inflammatory conditions.

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Data availability

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

The software used is commercially available.

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Acknowledgements

This work was supported by Grants from Iran National Science Foundation (INSF), Grant number 99029190 and Research Council of University of Isfahan. We are grateful to Professor Dr. Ilkay Erdogan Orhan for providing valuable comments.

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Authors and Affiliations

  1. Faculty of Biological Science and Technology, Department of Cell and Molecular Biology & Microbiology, University of Isfahan, Isfahan, Iran

    Morteza Sadeghi & Mehran Miroliaei

  2. Department of Chemistry, University of Isfahan, Isfahan, Iran

    Fatemeh Fateminasab

  3. Department of Biotechnology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran

    Mohammad Moradi

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  1. Morteza Sadeghi
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  2. Mehran Miroliaei
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  3. Fatemeh Fateminasab
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Contributions

Morteza Sadeghi (study conception and design, critical revision, and manuscript drafting), Mehran Miroliaei (supervision, study conception, critical revision, and design), Fatemeh Fateminasab (study conception, critical revision, and manuscript drafting), and Mohammad Moradi (Data analysis and revision of manuscript).

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Correspondence to Mehran Miroliaei.

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Sadeghi, M., Miroliaei, M., Fateminasab, F. et al. Screening cyclooxygenase-2 inhibitors from Allium sativum L. compounds: in silico approach. J Mol Model 28, 24 (2022). https://doi.org/10.1007/s00894-021-05016-4

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