title: Evaluation of polyphenols from Broussonetia papyrifera as coronavirus protease inhibitors.
abstract: The current study was designed to assess the inhibitory activity of Broussonetia papyrifera-derived polyphenols against 3-chymotrypsin-like and papain-like coronavirus cysteine proteases. The isolated compounds were broussochalcone B (1), broussochalcone A (2), 4-hydroxyisolonchocarpin (3), papyriflavonol A (4), 3'-(3-methylbut-2-enyl)-3',4,7-trihydroxyflavane (5), kazinol A (6), kazinol B (7), broussoflavan A (8), kazinol F (9), and kazinol J (10). All polyphenols were more potent against papain-like protease (PLpro) than against 3-chymotripsin-like protease (3CLpro); therefore, we investigated their structural features that were responsible for this selectivity. Compound 4 was the most potent inhibitor of PLprowith an IC50value of 3.7 μM. The active compounds displayed kinetic behaviors, and the binding constants of their interaction with PLprowere determined from surface plasmon resonance analysis. Our results suggest B. papyrifera constituents as promising candidates for development into potential anti-coronaviral agents.
authors.affiliation: a Natural Product Material Research Center, Korea Research Institute of Bioscience and Biotechnology , Jeongeup , Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: b Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology , Ochang , Republic of Korea.
authors.forename: Heung Joo
authors.initials: HJ
authors.lastname: Yuk
authors.affiliation: b Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology , Ochang , Republic of Korea.
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Ryu
authors.affiliation: a Natural Product Material Research Center, Korea Research Institute of Bioscience and Biotechnology , Jeongeup , Republic of Korea.
authors.forename: Su Hwan
authors.initials: SH
authors.lastname: Lim
authors.affiliation: a Natural Product Material Research Center, Korea Research Institute of Bioscience and Biotechnology , Jeongeup , Republic of Korea.
authors.forename: Kyung Su
authors.initials: KS
authors.lastname: Kim
authors.affiliation: c Division of Applied Life Science (BK21 program, IALS) , Graduate School of Gyeongsang National University , Jinju , Republic of Korea.
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
authors.affiliation: a Natural Product Material Research Center, Korea Research Institute of Bioscience and Biotechnology , Jeongeup , Republic of Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.affiliation: a Natural Product Material Research Center, Korea Research Institute of Bioscience and Biotechnology , Jeongeup , Republic of Korea.
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
mesh_terms: D031623:Broussonetia / Q000737:chemistry*; D017934:Coronavirus / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D009682:Magnetic Resonance Spectroscopy; D059808:Polyphenols / Q000302:isolation & purification*; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D059808:Polyphenols; D011480:Protease Inhibitors
keywords: Broussonetia papyrifera; SARS; coronavirus; papain-like protease; polyphenol