title: Diarylheptanoids from Alnus japonica inhibit papain-like protease of severe acute respiratory syndrome coronavirus.
abstract: The papain-like protease (PL(pro)), which controls replication of the severe acute respiratory syndrome coronavirus (SARS-CoV), has been identified as a potential drug target for the treatment of SARS. An intensive hunt for effective anti-SARS drugs has been undertaken by screening for natural product inhibitors that target SARS-CoV PL(pro). In this study, diarylheptanoids 1-9 were isolated from Alnus japonica, and the inhibitory activities of these compounds against PL(pro) were determined. Of the isolated diarylheptanoids, hirsutenone (2) showed the most potent PL(pro) inhibitory activity, with an inhibitory concentration (IC(50)) value of 4.1 µM. Structure-activity analysis showed that catechol and α,β-unsaturated carbonyl moiety in the molecule were the key requirement for SARS-CoV cysteine protease inhibition.
authors.affiliation: Infection Control Material Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 580–185, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Hyung Jae
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Jang Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Doman
authors.initials: D
authors.lastname: Kim
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Park
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
mesh_terms: D029661:Alnus; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000235:genetics; D036381:Diarylheptanoids / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D024301:Plant Bark; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D036381:Diarylheptanoids; D011480:Protease Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases