In our ongoing efforts to identify effective natural antiviral agents, four methoxy flavonoids (1-4) were isolated from the Inula britannica flower extract. Their structures were elucidated using nuclear magnetic resonance. Flavonoids 1-4 exhibited inhibitory activity against SARS- CoV-2 3CLpro with IC50 values of 41.6 ± 2.5, 35.9 ± 0.9, 32.8 ± 1.2, and 96.6 ± 3.4 μM, respectively. Flavonoids 1-3 inhibited 3CLpro in a competitive manner. Based on molecular simulations, key amino acids that form hydrogen bond with inhibitor 3 were identified. Finally, we found that inhibitors (1-3) suppressed HCoV-OC43 coronavirus proliferation at micromole concentrations.
Keywords: 3CLpro; HCoV-OC43; Inula britannica; Methoxyl flavonoids; SARS-CoV-2.
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