Bioorganic & Medicinal Chemistry
Volume 21, Issue 13, 1 July 2013, Pages 3730-3737
Ji-Young Park, Jang Hoon Kim, Jung Min Kwon, Hyung- Jun Kwon, Hyung Jae Jeong, Young Min Kim, Doman Kim, Woo Song Lee, Young Bae Ryu
Abstract
SARS-CoV 3CLpro plays an important role in viral replication. In this study, we performed a biological evaluation on nine phlorotannins isolated from the edible brown algae Ecklonia cava. The nine isolated phlorotannins (1–9), except phloroglucinol (1), possessed SARS-CoV 3CLpro inhibitory activities in a dose-dependently and competitive manner. Of these phlorotannins (1–9), two eckol groups with a diphenyl ether linked dieckol (8) showed the most potent SARS-CoV 3CLpro trans/cis-cleavage inhibitory effects (IC50s = 2.7 and 68.1 μM, respectively). This is the first report of a (8) phlorotannin chemotype significantly blocking the cleavage of SARS-CoV 3CLpro in a cell-based assay with no toxicity. Furthermore, dieckol (8) exhibited a high association rate in the SPR sensorgram and formed extremely strong hydrogen bonds to the catalytic dyad (Cys145 and His41) of the SARS-CoV 3CLpro.
Keywords
Phlorotannin, SARS-CoV, Dieckol, Eckol, Ecklonia cava