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. 2010 Nov 15;18(22):7940-7.
doi: 10.1016/j.bmc.2010.09.035. Epub 2010 Sep 19.

Biflavonoids From Torreya Nucifera Displaying SARS-CoV 3CL(pro) Inhibition

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Biflavonoids From Torreya Nucifera Displaying SARS-CoV 3CL(pro) Inhibition

Young Bae Ryu et al. Bioorg Med Chem. .
Free PMC article

Abstract

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

Figures

None
Figure 1
Figure 1
(A) HPLC total chromatogram of EtOH extract of T. nucifera. HPLC chromatograms of hexane (B) and EtOAc fraction (C) of T. nucifera leaves extract.
Figure 2
Figure 2
Chemical structures of isolated compounds (112) from leaves of the T. nucifera.
Figure 3
Figure 3
Effects of diterpenoids (18, A) and biflavones (912, B) on the activity of SARS-CoV 3CLpro.
Figure 4
Figure 4
Chemical structures of apigenin, luteolin, quercetin, and amentoflavone (9).
Figure 5
Figure 5
(A) Dixon plot for inhibition of amentoflavone (9) on 3CLpro for the proteolysis of substrate. In the presence of difference concentrations of substrate: 2.5 μM (▾), 5.0 μM (○), and 10.0 μM (●). (B) The plot of Vmax versus inhibitor concentrations for determining the inhibition type.
Figure 6
Figure 6
The binding pose of amentoflavone (9) in SARS-CoV 3CLpro. Ribbon plot of 9 complexed to 3CLpro with hydrogen bonding.

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References

    1. Berger A., Drosten C., Doerr H.W., Sturmer M., Preiser W. J. Clin. Virol. 2004;29:13. - PMC - PubMed
    1. Stadler K., Masignani V., Eickmann M., Becker S., Abrignani S., Klenk H.D., Rappuoli R. Nat. Rev. Microbiol. 2003;1:209. - PMC - PubMed
    1. Drosten C., Gunther S., Preiser W., van der Werf S., Brodt H.R., Becker S., Rabenau H., Panning M., Kolesnikova L., Fouchier R.A., Berger A., Burguiere A.M., Cinatl J., Eickmann M., Escriou N., Grywna K., Kramme S., Manuguerra J.C., Muller S., Rickerts V., Sturmer M., Vieth S., Klenk H.D., Osterhaus A.D., Schmitz H., Doerr H.W. N. Eng. J. Med. 2003;348:1967. - PubMed
    1. Peiris J.S., Lai S.T., Poon L.L., Guan Y., Yam L.Y., Lim W., Nicholls J., Yee W.K., Yan W.W., Cheung M.T., Cheng V.C., Chan K.H., Tsang D.N., Yung R.W., Ng T.K., Yuen K.Y. Lancet. 2003;361:1319. - PMC - PubMed
    1. Rota P.A., Oberste M.S., Nix W.A., Campagnoli R., Icenogle J.P., Penaranda S., Bankamp B., Maher K., Chen M.-H., Tong S., Tamin A., Lowe L., Frace M., De Risi J.L., Chen Q., Wang D., Erdman D.D., Peret T.C.T., Burns C., Ksiazek T.G., Rollin P.E., Sanchez A., Liffick S., Holloway B., Limor J., McCaustland K., Olsen-Rasmussen M., Fouchier R., Gunther S., Osterhaus A.D.H.E., Drosten C., Pallansch M.A., Anderson L.J., Bellini W.J. Science. 2003;300:1394. - PubMed

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