Covid-19 disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global epidemic that affects millions of lives. To date, there is no definitive cure for the disease and global vaccination efforts with newly produced vaccines will take years to complete. In silico studies have suggested that different flavonoids play an antiviral role against SARS-CoV-2. In this study, based on in silico findings, we examined the in vitro effects of four promising flavonoids, hesperidin, oleuropein, epigallocatechin gallate (EGCG), and myricetin. Material and Methods: Hesperidin, oleuropein, EGCG, and myricetin have been extracted from natural plant sources and purified by using liquid chromatography (LC). Analyses of the cell toxicity and antiviral activity of these four flavonoids at different concentrations against SARS-CoV-2 were done. Results: Our results show that CC50 values for EGCG, hesperidin, myricetin and oleuropein are 38 μg/ml, 25 μg/ml, >200 μg/ml and >200 μg/ml, respectively. In addition, in our hands, neither of the flavonoids we examined has antiviral effects against Sars-CoV-2 virus-infected Vero E6 cells. Our data revealed that all flavonoids we tested have Inhibitory Concentration 50 (IC50) value >200 μg/ml. Conclusion: Our results using the SARS-CoV-2 infected Vero E6 cell model were found to contradict previous in silico findings, and these flavonoids were found to have no antiviral effects in vitro. Studies investigating flavonoids' antiviral activity on SARS-CoV-2 should be directed to those other than oleuropein, hesperidin, EGCG, and myricetin.
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