Bisflavonoids from Torreya nucifera displaying SARS-CoV 3CLpro inhibition = 비자로부터 사스코로나 3CL효소를 억제하는 비스플라보노이드계 화합물의 개발

Abstract

As part of our search for botanical sources of SARS-CoV 3CLpro inhibitors, we selected Torreya nucifera, which is traditionally used as a medicinal plant in Asia. The ethanol extract of T. nucifera leaves exhibited good SARS-CoV 3CLpro inhibitory activity (62% at 100 μg/mL). Following bioactivity-guided fractionation, eight diterpenoids (1-8) and four biflavonoids (9-12) were isolated and evaluated for SARS-CoV 3CLpro inhibition using fluorescence resonance energy transfer analysis. of these compounds, the biflavone amentoflavone (9) (IC50 = 8.3 μM) showed most potent 3CLpro inhibitory effect. Three additional authentic flavones (apigenin, luteolin and quercetin) were tested to establish the basic structure-activity relationship of biflavones. Apigenin, luteolin, and quercetin inhibited 3CLpro activity with IC50 values of 280.8, 20.2, and 23.8 μM, respectively. Values of binding energy obtained in a molecular docking study supported the results of enzymatic assays. More potent activity appeared to be associated with the presence of an apigenin moiety at position C-3′ of flavones, as biflavone had an effect on 3CLpro inhibitory activity.