title: Influenza virus neuraminidase inhibitory activity of phlorotannins from the edible brown alga Ecklonia cava.
abstract: Influenza A virus infections continue to pose a major threat to humans and several animal species. Neuraminidase (NA) is one of the most promising targets for the development of drugs against influenza viruses because of its critical role in the viral life cycle. During the course of a search for NA inhibitors from edible natural sources, we found that the ethyl acetate layer of ethanol extracts of Ecklonia cava showed extremely high NA-inhibitory activity (72.1% inhibition at 30 μg/mL). Bioactivity-guided fractionation of the ethyl acetate layer yielded five phlorotannins, identified as phloroglucinol (1), eckol (2), 7-phloroeckol (3), phlorofucofuroeckol (4), and dieckol (5). The inhibitory activities of these compounds (1-5) against NAs from group-1 (A/Bervig_Mission/1/18 [H1N1], A/PR/8/34 [H1N1]) and group-2 (A/Hong Kong/8/68 [H3N2], A/Chicken/Korea/MS96/96 [H9N2]) influenza A were evaluated to determine potencies and kinetic behavior. Analyses using various in vitro influenza A virus NA assays showed that all five phlorotannin derivatives were selective NA inhibitors. Of the phlorotannins, phlorofucofuroeckol (4) exhibited the most potent inhibitory activities toward group-1 NAs (IC₅₀ values, 4.5 and 14.7 μM), whereas dieckol (5) potently inhibited group-2 NAs. Kinetic analyses indicated that compounds 1-5 were all noncompetitive. Notably, these noncompetitive inhibitors synergized with oseltamivir to enhance the NA-inhibitory effects of oseltamivir.
authors.affiliation: Eco-Friendly Biomaterial Research Center and AI Control Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup 580-185, Republic of Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Ryu
authors.forename: Hyung Jae
authors.initials: HJ
authors.lastname: Jeong
authors.forename: So Young
authors.initials: SY
authors.lastname: Yoon
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Young Min
authors.initials: YM
authors.lastname: Kim
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Mun-Chual
authors.initials: MC
authors.lastname: Rho
authors.forename: Se-Jae
authors.initials: SJ
authors.lastname: Kim
authors.forename: Woo Song
authors.initials: WS
authors.lastname: Lee
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects / Q000201:enzymology; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D007700:Kinetics; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D000459:Phaeophyceae / Q000737:chemistry*; D013634:Tannins / Q000737:chemistry / Q000494:pharmacology*; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D013634:Tannins; D014764:Viral Proteins; C487630:NA protein, influenza A virus; D009439:Neuraminidase