Details

Autor(en) / Beteiligte

• El Hassab, Mahmoud A.
• Eldehna, Wagdy M.
• Al-Rashood, Sara T.
• Alharbi, Amal
• Eskandrani, Razan O.
• Alkahtani, Hamad M.
• Elkaeed, Eslam B.
• Abou-Seri, Sahar M.

Titel

Multi-stage structure-based virtual screening approach towards identification of potential SARS-CoV-2 NSP13 helicase inhibitors

Ist Teil von

• Journal of enzyme inhibition and medicinal chemistry, 2022-12, Vol.37 (1), p.563-572

Ort / Verlag

England: Taylor & Francis

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• On account of its crucial role in the virus life cycle, SARS-COV-2 NSP13 helicase enzyme was exploited as a promising target to identify a novel potential inhibitor using multi-stage structure-based drug discovery approaches. Firstly, a 3D pharmacophore was generated based on the collected data from a protein-ligand interaction fingerprint (PLIF) study using key interactions between co-crystallised fragments and the NSP13 helicase active site. The ZINC database was screened through the generated 3D-pharmacophore retrieving 13 potential hits. All the retrieved hits exceeded the benchmark score of the co-crystallised fragments at the molecular docking step and the best five-hit compounds were selected for further analysis. Finally, a combination between molecular dynamics simulations and MM-PBSA based binding free energy calculations was conducted on the best hit (compound FWM-1) bound to NSP13 helicase enzyme, which identified FWM-1 as a potential potent NSP13 helicase inhibitor with binding free energy equals −328.6 ± 9.2 kcal/mol.