Evaluation of polyphenols from Broussonetia papyrifera as coronavirus protease inhibitors

被引:265
作者
Park, Ji-Young [1 ]
Yuk, Heung Joo [2 ]
Ryu, Hyung Won [2 ]
Lim, Su Hwan [1 ]
Kim, Kyung Su [1 ]
Park, Ki Hun [3 ]
Ryu, Young Bae [1 ]
Lee, Woo Song [1 ]
机构
[1] Korea Res Inst Biosci & Biotechnol, Nat Prod Mat Res Ctr, Jeongeup 580185, South Korea
[2] Korea Res Inst Biosci & Biotechnol, Nat Med Res Ctr, Ochang, South Korea
[3] Gyeongsang Natl Univ, Grad Sch, Program BK21, Div Appl Life Sci,IALS, Jinju, South Korea
关键词
Broussonetia papyrifera; coronavirus; papain-like; protease; polyphenol; SARS; RESPIRATORY SYNDROME CORONAVIRUS; PAPAIN-LIKE PROTEASE; SARS-COV 3CL(PRO);
D O I
10.1080/14756366.2016.1265519
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (3CL(pro)); therefore, we investigated their structural features that were responsible for this selectivity. Compound 4 was the most potent inhibitor of PLpro with an IC50 value of 3.7 mu M. The active compounds displayed kinetic behaviors, and the binding constants of their interaction with PLpro were determined from surface plasmon resonance analysis. Our results suggest B. papyrifera constituents as promising candidates for development into potential anti-coronaviral agents.
引用
收藏
页码:504 / 512
页数:9
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