Back to Search
Start Over
Rutin and flavone analogs as prospective SARS-CoV-2 main protease inhibitors: In silico drug discovery study
- Source :
- Journal of Molecular Graphics & Modelling
- Publication Year :
- 2021
- Publisher :
- Elsevier Inc., 2021.
-
Abstract
- Coronavirus disease 2019 (COVID-19) is a new pandemic characterized by quick spreading and illness of the respiratory system. To date, there is no specific therapy for Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). Flavonoids, especially rutin, have attracted considerable interest as a prospective SARS-CoV-2 main protease (Mpro) inhibitor. In this study, a database containing 2017 flavone analogs was prepared and screened against SARS-CoV-2 Mpro using the molecular docking technique. According to the results, 371 flavone analogs exhibited good potency towards Mpro with docking scores less than −9.0 kcal/mol. Molecular dynamics (MD) simulations, followed by molecular mechanics-generalized Born surface area (MM/GBSA) binding energy calculations, were performed for the top potent analogs in complex with Mpro. Compared to rutin, PubChem-129-716-607 and PubChem-885-071-27 showed better binding affinities against SARS-CoV-2 Mpro over 150 ns MD course with ΔGbinding values of −69.0 and −68.1 kcal/mol, respectively. Structural and energetic analyses demonstrated high stability of the identified analogs inside the SARS-CoV-2 Mpro active site over 150 ns MD simulations. The oral bioavailabilities of probable SARS-CoV-2 Mpro inhibitors were underpinned using drug-likeness parameters. A comparison of the binding affinities demonstrated that the MM/GBSA binding energies of the identified flavone analogs were approximately three and two times less than those of lopinavir and baicalein, respectively. In conclusion, PubChem-129-716-607 and PubChem-885-071-27 are promising anti-COVID-19 drug candidates that warrant further clinical investigations.<br />Graphical abstract Image 1
- Subjects :
- 0301 basic medicine
030103 biophysics
medicine.medical_treatment
In silico
Rutin
Pharmacology
Molecular dynamics
Molecular Docking Simulation
Flavones
Article
03 medical and health sciences
chemistry.chemical_compound
SARS-CoV-2 main protease
Drug Discovery
Materials Chemistry
medicine
Humans
Protease Inhibitors
Prospective Studies
Physical and Theoretical Chemistry
Spectroscopy
chemistry.chemical_classification
Protease
Drug discovery
SARS-CoV-2
COVID-19
Computer Graphics and Computer-Aided Design
Baicalein
030104 developmental biology
chemistry
Docking (molecular)
Molecular docking
Drug-likeness
Subjects
Details
- Language :
- English
- ISSN :
- 18734243 and 10933263
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Graphics & Modelling
- Accession number :
- edsair.doi.dedup.....d73149bcd59022b8a49dd679bdb9f156