Rational design of flavonoid based potential inhibitors targeting SARS-CoV 3CL protease for the treatment of COVID-19
| Autor: | Joginder Singh, Vikas Kaushik, Shipra Bhati |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.drug_class
medicine.medical_treatment Pharmacology 010402 general chemistry 01 natural sciences Article Analytical Chemistry 3CL protease Inorganic Chemistry chemistry.chemical_compound Pharmacokinetics medicine Spectroscopy Protease SARS-CoV-2 010405 organic chemistry Chemistry Organic Chemistry Rational design COVID-19 Ligand (biochemistry) 0104 chemical sciences Bioavailability Docking (molecular) Molecular docking Flavonoid Lactam Antiviral drug |
| Zdroj: | Journal of Molecular Structure |
| ISSN: | 0022-2860 |
| Popis: | The current outbreak of Coronavirus Disease 2019 (COVID-19) pandemic has reported thousands of deaths worldwide due to the rapid transmission rate and the lack of antiviral drugs and vaccinations. There is an urgent need to develop potential antiviral drug candidates for the prevention of COVID-19 infection. In the present study, a series of potential inhibitors targeting SARS-CoV 3CL protease were rationally designed by incorporating gamma lactam ring, and various fluoro substituted heterocyclic ring systems to the flavonoid scaffold. The prediction of drug-likeness, oral bioavailability, toxicity, synthetic accessibility, and ADMET properties was made by computational means. Quercetin was used as standard. The binding affinity of the ligands towards the 3CL protease target was examined using docking simulations. The designed ligands possess favourable pharmacokinetic and pharmacodynamic properties. Ligand L4, L8, and L14 appeared to be the lead compounds in the series and can be considered for further in-vivo and in-vitro validation. Graphical abstract Image, graphical abstract |
| Databáze: | OpenAIRE |
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