Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL super(pro) inhibition

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 22; pp. 7940 - 7947
• Main Authors: Ryu, Young Bae, Jeong, Hyung Jae, Kim, Jang Hoon, Kim, Young Min, Park, Ji-Young, Kim, Doman, Naguyen, Thi Thanh Hanh, Park, Su-Jin, Chang, Jong Sun, Park, Ki Hun, Rho, Mun-Chual, Lee, Woo Song
• Format: Journal Article
• Language: English
• Published: 15.11.2010
• Subjects: Ethanol; SARS coronavirus
• ISSN: 0968-0896
• DOI: 10.1016/j.bmc.2010.09.035

As part of our search for botanical sources of SARS-CoV 3CL super(pro) 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 3CL super(pro) inhibitory activity (62% at 100 kg/mL). Following bioactivity-guided fractionation, eight diterpenoids ( 1- 8) and four biflavonoids ( 9- 12) were isolated and evaluated for SARS-CoV 3CL super(pro) inhibition using fluorescence resonance energy transfer analysis. Of these compounds, the biflavone amentoflavone ( 9) (IC sub(50) = 8.3 kM) showed most potent 3CL super(pro) 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 3CL super(pro) activity with IC sub(50) values of 280.8, 20.2, and 23.8 kM, 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 3CL super(pro) inhibitory activity.