Natural polyphenolic drugs were approved for treatment of various diseases. Diosmin, rutin, quercetin, aesculin, genistein, hesperidin and silybin are known for their safety and have been applied for several human disorders including cancer, cardiovascular disorders, atherosclerosis, oxidative stress, capillary fragility, liver and pancreatic disorders and others. As the structures of the selected polyphenolic compounds possess variable chemical moieties with diverse chemical and electronic characters, these properties have been employed for further insights studies to predict new applications concerning the newly occurred pandemic. COVID-19 is a terrible disease that attacked millions of human populations at the end of year 2019. As the number of death cases has increased to exceed one million of humans, the early discovery of new treatment from previously approved and safe drugs is the main target of this study. Employing the putative docking studies for the selected polyphenolic drugs were done and the results were promising, all tested drugs exhibited high affinity with the selected five proteins of protease enzyme, the docking score ranged from -8.4461 to -26.1691 kcal/mol with 3-7 variable interaction bonds. Among the tested drugs, diosmin appeared as the most promising drug as it exhibited the highest energy score and interaction bonds with the most of proteins.
