Using in silico modelling and FRET-based assays in the discovery of novel FDA-approved drugs as inhibitors of MERS-CoV helicase
| Autor: | Mohamed Boudjelal, Imadul Islam, A S Askar, Sheraz Gul, A O Adedeji, Nimer Mehyar, Abdullah Mashhour |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2021 |
| Předmět: |
Quantitative structure–activity relationship
In silico Quantitative Structure-Activity Relationship Bioengineering Virus Replication medicine.disease_cause Antiviral Agents 01 natural sciences Drug Discovery medicine Humans Enzyme Inhibitors Coronavirus chemistry.chemical_classification biology SARS-CoV-2 010405 organic chemistry Chemistry Drug discovery DNA Helicases Helicase General Medicine COVID-19 Drug Treatment 0104 chemical sciences 010404 medicinal & biomolecular chemistry Enzyme Förster resonance energy transfer Biochemistry Docking (molecular) Middle East Respiratory Syndrome Coronavirus biology.protein Molecular Medicine Coronavirus Infections |
| Zdroj: | SAR and QSAR in Environmental Research |
| DOI: | 10.6084/m9.figshare.13525564.v1 |
| Popis: | A Förster resonance energy transfer (FRET)-based assay was used to screen the FDA-approved compound library against the MERS-CoV helicase, an essential enzyme for virus replication within the host cell. Five compounds inhibited the helicase activity with submicromolar potencies (IC50, 0.73–1.65 µM) and ten compounds inhibited the enzyme with micromolar potencies (IC50, 19.6–502 µM). The molecular operating environment (MOE) was used to dock the identified inhibitors on the MERS-CoV helicase nucleotide binding. Strong inhibitors docked well in the nucleotide-binding site and established interactions with some of the essential residues. There was a reasonable correlation between the observed IC50 values and the MOE docking scores of the strong inhibitors (r2 = 0.74), indicating the ability of the in silico docking model to predict the binding of strong inhibitors. In silico docking could be a useful complementary tool used with the FRET-based assay to predict new MERS-CoV helicase inhibitors. The identified inhibitors could potentially be used in the clinical development of new antiviral treatment for MERS-CoV and other coronavirus related diseases, including coronavirus disease 2019 (COVID-19). |
| Databáze: | OpenAIRE |
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