In silico pharmacokinetic and molecular docking studies of natural flavonoids and synthetic indole chalcones against essential proteins of SARS-CoV-2.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is distinctly infective and there is an ongoing effort to find a cure for this pandemic. Flavonoids exist in many diets as well as in traditional medicine, and their modern subset, indole-chalcones, are effective in fighting various diseases. Hence, these flavonoids and structurally similar indole chalcones derivatives were studied in silico for their pharmacokinetic properties including absorption, distribution, metabolism, excretion, toxicity (ADMET) and anti-SARS-CoV-2 properties against their proteins, namely, RNA dependent RNA polymerase (rdrp), main protease (Mpro) and Spike (S) protein via homology modelling and docking. Interactions were studied with respect to biology and function of SARS-CoV-2 proteins for activity. Functional/structural roles of amino acid residues of SARS-CoV-2 proteins and, the effect of flavonoid and indole chalcone interactions which may cause disease suppression are discussed. The results reveal that out of 23 natural flavonoids and 25 synthetic indole chalcones, 30 compounds are capable of Mpro deactivation as well as potentially lowering the efficiency of Mpro function. Cyanidin may inhibit RNA polymerase function and, Quercetin is found to block interaction sites on the viral spike. These results suggest flavonoids and their modern pharmaceutical cousins, indole chalcones are capable of fighting SARS-CoV-2. The in vitro anti-SARS-CoV-2 activity of these 30 compounds needs to be studied further for complete understanding and confirmation of their inhibitory potential.
['Vijayakumar|Balaji Gowrivel|BG|', 'Ramesh|Deepthi|D|', 'Joji|Annu|A|', 'Jayachandra Prakasan|Jayadharini|J|', 'Kannan|Tharanikkarasu|T|']
D000073640:Betacoronavirus D047188:Chalcones D003198:Computer Simulation D005419:Flavonoids D007211:Indoles D062105:Molecular Docking Simulation D011487:Protein Conformation D000086402:SARS-CoV-2 D012449:Safety D014018:Tissue Distribution D014764:Viral Proteins
In silico Flavonoids Indole chalcones SARS-CoV-2 COVID-19 Phytochemicals