title: Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds.
abstract: The 3C-like protease (3CLpro) of SARS-coronavirus mediates the proteolytic processing of replicase polypeptides 1a and 1ab into functional proteins, becoming an important target for the drug development. In this study, Isatis indigotica root extract, five major compounds of I. indigotica root, and seven plant-derived phenolic compounds were tested for anti-SARS-CoV 3CLpro effects using cell-free and cell-based cleavage assays. Cleavage assays with the 3CLpro demonstrated that IC50 values were in micromolar ranges for I. indigotica root extract, indigo, sinigrin, aloe emodin and hesperetin. Sinigrin (IC50: 217 microM) was more efficient in blocking the cleavage processing of the 3CLpro than indigo (IC50: 752 microM) and beta-sitosterol (IC50: 1210 microM) in the cell-based assay. Only two phenolic compounds aloe emodin and hesperetin dose-dependently inhibited cleavage activity of the 3CLpro, in which the IC50 was 366 microM for aloe emodin and 8.3 microM for hesperetin in the cell-based assay.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 91 Hsueh-Shih Road, Taichung 404, Taiwan, ROC. cwlin@mail.cum.edu.tw
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Lai
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
authors.forename: Tin-Yun
authors.initials: TY
authors.lastname: Ho
authors.forename: Chang-Chi
authors.initials: CC
authors.lastname: Hsieh
authors.forename: Pei-Dawn Lee
authors.initials: PD
authors.lastname: Chao
mesh_terms: D000818:Animals; D000880:Anthraquinones; D002522:Chlorocebus aethiops; D004396:Coloring Agents / Q000737:chemistry / Q000494:pharmacology; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases; D004642:Emodin / Q000737:chemistry / Q000494:pharmacology; D010450:Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005961:Glucosinolates / Q000737:chemistry / Q000494:pharmacology; D006569:Hesperidin / Q000737:chemistry / Q000494:pharmacology; D007203:Indigo Carmine; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D031219:Isatis / Q000737:chemistry*; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D014709:Vero Cells / Q000378:metabolism; D014764:Viral Proteins / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D005961:Glucosinolates; D007211:Indoles; D010636:Phenols; D010936:Plant Extracts; D014764:Viral Proteins; C010330:sinigrin; C518327:aloe emodin; D007203:Indigo Carmine; D006569:Hesperidin; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases; D004642:Emodin; C013015:hesperetin