Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2
Owing to the urgent need for therapeutic interventions against the SARS-coronavirus 2 (SARS-CoV-2) pandemic, we employed an in silico approach to evaluate the SARS-CoV-2 inhibitory potential of newly synthesized imidazoles. The inhibitory potentials of the compounds against SARS-CoV-2 drug targets -...
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doaj-97da492767d64f65a31f15ad903b055d2021-07-21T04:10:31ZengElsevierJournal of Pharmacological Sciences1347-86132021-09-0114716271Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2Titilayo O. Johnson0Abayomi Emmanuel Adegboyega1Opeyemi Iwaloye2Omokehinde Abiodun Eseola3Winfried Plass4Boluwatife Afolabi5Damilare Rotimi6Eman I. Ahmed7Ashraf Albrakati8Gaber E. Batiha9Oluyomi Stephen Adeyemi10Department of Biochemistry, Faculty of Basic Medical Sciences, University of Jos, Jos, Nigeria; Corresponding author.Department of Biochemistry, Faculty of Basic Medical Sciences, University of Jos, Jos, NigeriaBioinformatics and Molecular Biology Unit, Department of Biochemistry, Federal University of Technology, AkureDepartment of Chemical Sciences, Redeemer's University, Ede, Nigeria; Friedrich-Schiller-Universität Jena, Institute of Inorganic and Analytical Chemistry, Humboldtstraße 8, 07743, Jena, GermanyFriedrich-Schiller-Universität Jena, Institute of Inorganic and Analytical Chemistry, Humboldtstraße 8, 07743, Jena, GermanyDepartment of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Landmark University, PMB 1001, Omu-Aran -, 251101, NigeriaDepartment of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Landmark University, PMB 1001, Omu-Aran -, 251101, NigeriaDepartment of Pharmacology and Therapeutics, College of Medicine, Jouf University, Sakaka, 72346, Saudi Arabia; Department of Pharmacology, Faculty of Medicine, Fayoum University, Fayoum, 63511, EgyptDepartment of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif, 21944, Saudi ArabiaDepartment of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, EgyptDepartment of Biochemistry, Medicinal Biochemistry, Nanomedicine & Toxicology Laboratory, Landmark University, PMB 1001, Omu-Aran -, 251101, Nigeria; Corresponding author.Owing to the urgent need for therapeutic interventions against the SARS-coronavirus 2 (SARS-CoV-2) pandemic, we employed an in silico approach to evaluate the SARS-CoV-2 inhibitory potential of newly synthesized imidazoles. The inhibitory potentials of the compounds against SARS-CoV-2 drug targets - main protease (Mpro), spike protein (Spro) and RNA-dependent RNA polymerase (RdRp) were investigated through molecular docking analysis. The binding free energy of the protein-ligand complexes were estimated, pharmacophore models were generated and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the compounds were determined. The compounds displayed various levels of binding affinities for the SARS-CoV-2 drug targets. Bisimidazole C2 scored highest against all the targets, with its aromatic rings including the two imidazole groups contributing to the binding. Among the phenyl-substituted 1H-imidazoles, C9 scored highest against all targets. C11 scored highest against Spro and C12 against Mpro and RdRp among the thiophene-imidazoles. The compounds interacted with HIS 41 - CYS 145 and GLU 288 – ASP 289 – GLU 290 of Mpro, ASN 501 of Spro receptor binding motif and some active site amino acids of RdRp. These novel imidazole compounds could be further developed as drug candidates against SARS-CoV-2 following lead optimization and experimental studies.http://www.sciencedirect.com/science/article/pii/S1347861321000463Drug discoveryDrug targetMolecular dockingCoronavirus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Titilayo O. Johnson Abayomi Emmanuel Adegboyega Opeyemi Iwaloye Omokehinde Abiodun Eseola Winfried Plass Boluwatife Afolabi Damilare Rotimi Eman I. Ahmed Ashraf Albrakati Gaber E. Batiha Oluyomi Stephen Adeyemi |
spellingShingle |
Titilayo O. Johnson Abayomi Emmanuel Adegboyega Opeyemi Iwaloye Omokehinde Abiodun Eseola Winfried Plass Boluwatife Afolabi Damilare Rotimi Eman I. Ahmed Ashraf Albrakati Gaber E. Batiha Oluyomi Stephen Adeyemi Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2 Journal of Pharmacological Sciences Drug discovery Drug target Molecular docking Coronavirus |
author_facet |
Titilayo O. Johnson Abayomi Emmanuel Adegboyega Opeyemi Iwaloye Omokehinde Abiodun Eseola Winfried Plass Boluwatife Afolabi Damilare Rotimi Eman I. Ahmed Ashraf Albrakati Gaber E. Batiha Oluyomi Stephen Adeyemi |
author_sort |
Titilayo O. Johnson |
title |
Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2 |
title_short |
Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2 |
title_full |
Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2 |
title_fullStr |
Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2 |
title_full_unstemmed |
Computational study of the therapeutic potentials of a new series of imidazole derivatives against SARS-CoV-2 |
title_sort |
computational study of the therapeutic potentials of a new series of imidazole derivatives against sars-cov-2 |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2021-09-01 |
description |
Owing to the urgent need for therapeutic interventions against the SARS-coronavirus 2 (SARS-CoV-2) pandemic, we employed an in silico approach to evaluate the SARS-CoV-2 inhibitory potential of newly synthesized imidazoles. The inhibitory potentials of the compounds against SARS-CoV-2 drug targets - main protease (Mpro), spike protein (Spro) and RNA-dependent RNA polymerase (RdRp) were investigated through molecular docking analysis. The binding free energy of the protein-ligand complexes were estimated, pharmacophore models were generated and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the compounds were determined. The compounds displayed various levels of binding affinities for the SARS-CoV-2 drug targets. Bisimidazole C2 scored highest against all the targets, with its aromatic rings including the two imidazole groups contributing to the binding. Among the phenyl-substituted 1H-imidazoles, C9 scored highest against all targets. C11 scored highest against Spro and C12 against Mpro and RdRp among the thiophene-imidazoles. The compounds interacted with HIS 41 - CYS 145 and GLU 288 – ASP 289 – GLU 290 of Mpro, ASN 501 of Spro receptor binding motif and some active site amino acids of RdRp. These novel imidazole compounds could be further developed as drug candidates against SARS-CoV-2 following lead optimization and experimental studies. |
topic |
Drug discovery Drug target Molecular docking Coronavirus |
url |
http://www.sciencedirect.com/science/article/pii/S1347861321000463 |
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