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. 2012 Jun 15;22(12):4049-54.
doi: 10.1016/j.bmcl.2012.04.081. Epub 2012 Apr 25.

Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13

Mi-Sun Yu  1 , June Lee, Jin Moo Lee, Younggyu Kim, Young-Won Chin, Jun-Goo Jee, Young-Sam Keum, Yong-Joo Jeong
Affiliations

Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13

Mi-Sun Yu et al. Bioorg Med Chem Lett. .

Abstract

Severe acute respiratory syndrome (SARS) is an infectious disease with a strong potential for transmission upon close personal contact and is caused by the SARS-coronavirus (CoV). However, there are no natural or synthetic compounds currently available that can inhibit SARS-CoV. We examined the inhibitory effects of 64 purified natural compounds against the activity of SARS helicase, nsP13, and the hepatitis C virus (HCV) helicase, NS3h, by conducting fluorescence resonance energy transfer (FRET)-based double-strand (ds) DNA unwinding assay or by using a colorimetry-based ATP hydrolysis assay. While none of the compounds, examined in our study inhibited the DNA unwinding activity or ATPase activity of human HCV helicase protein, we found that myricetin and scutellarein potently inhibit the SARS-CoV helicase protein in vitro by affecting the ATPase activity, but not the unwinding activity, nsP13. In addition, we observed that myricetin and scutellarein did not exhibit cytotoxicity against normal breast epithelial MCF10A cells. Our study demonstrates for the first time that selected naturally-occurring flavonoids, including myricetin and scultellarein might serve as SARS-CoV chemical inhibitors.

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Figures

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Graphical abstract
Figure 1
Figure 1
(A) Schematic representation of FRET-based dsDNA unwinding assay. (B) Inhibition of the dsDNA unwinding activity of the SARS CoV helicase in the presence of 10 μM natural compounds. (C) Inhibition of the dsDNA unwinding activity of the HCV helicase in the presence of 10 μM natural compounds.
Figure 2
Figure 2
(A) Schematic representation of the ATP hydrolysis assay. (B) Inhibition of the ATP hydrolysis activity of the SARS CoV helicase in the presence of 10 μM natural compounds. (C) Inhibition of the ATP hydrolysis activity of the HCV helicase in the presence of 10 μM natural compounds
Figure 3
Figure 3
(A) Structure of myricetin and scutellarein. (B) IC50 value of nsP13 ATPase activity by myricetin and scutellarein. (C) The effects of myricetin and scutellarein on the growth of normal breast epithelial MCF10A cells.
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    1. Natural compounds used in our study were directly purified from various medicinal plants or purchased from commercial vendor (Chromadex Inc.) (Table 1). The integrity of the individual natural compounds, directly purified from natural plants was confirmed by NMR spectroscopy (More specific information is available upon request.). All natural compounds were dissolved in DMSO at a concentration of 10 mM as a stock solution before experiments.

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