title: Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13.
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.
authors.affiliation: Department of Bio and Nanochemistry, Kookmin University, Seoul 136-702, Republic of Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Yu
authors.forename: June
authors.initials: J
authors.lastname: Lee
authors.forename: Jin Moo
authors.initials: JM
authors.lastname: Lee
authors.forename: Younggyu
authors.initials: Y
authors.lastname: Kim
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Chin
authors.forename: Jun-Goo
authors.initials: JG
authors.lastname: Jee
authors.forename: Young-Sam
authors.initials: YS
authors.lastname: Keum
authors.forename: Yong-Joo
authors.initials: YJ
authors.lastname: Jeong
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology*; D001940:Breast / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003124:Colorimetry; D004247:DNA / Q000737:chemistry; D004265:DNA Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D031541:Fluorescence Resonance Energy Transfer; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D020365:RNA Helicases; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000201:enzymology; D013045:Species Specificity; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D005419:Flavonoids; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C040015:myricetin; D047310:Apigenin; D000255:Adenosine Triphosphate; D004247:DNA; D008780:Methyltransferases; C504965:Nsp13 protein, SARS-CoV; D004265:DNA Helicases; D020365:RNA Helicases; C458179:scutellarein