Počet záznamů: 1
Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors
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SYSNO ASEP 0539161 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors Tvůrce(i) Zima, V. (CZ)
Radilova, K. (CZ)
Kožíšek, M. (CZ)
Albinana, C. B. (CZ)
Karlukova, E. (CZ)
Brynda, Jiří (UMG-J) RID
Fanfrlik, J. (CZ)
Flieger, M. (CZ)
Hodek, J. (CZ)
Weber, J. (CZ)
Majer, P. (CZ)
Konvalinka, J. (CZ)
Machara, A. (CZ)Celkový počet autorů 13 Číslo článku 112754 Zdroj.dok. European Journal of Medicinal Chemistry. - : Elsevier - ISSN 0223-5234
Roč. 208, December (2020)Poč.str. 23 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. FR - Francie Klíč. slova Influenza ; Neuraminidase ; Polyphenols ; PA(N) endonuclease Inhibitors ; RNA polymerase Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 UT WOS 000600384300014 DOI 10.1016/j.ejmech.2020.112754 Anotace The biological effects of flavonoids on mammal cells are diverse, ranging from scavenging free radicals and anti-cancer activity to anti-influenza activity. Despite appreciable effort to understand the anti-influenza activity of flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. Here, we report the development and validation of a screening assay based on AlphaScreen technology and illustrate its application for determination of the inhibitory potency of a large set of polyols against PA N-terminal domain (PA-Nter) of influenza RNA-dependent RNA polymerase featuring endonuclease activity. The most potent inhibitors we identified were luteolin with an IC50 of 72 +/- 2 nM and its 8-C-glucoside orientin with an IC50 of 43 +/- 2 nM. Submicromolar inhibitors were also evaluated by an in vitro endonuclease activity assay using single-stranded DNA, and the results were in full agreement with data from the competitive AlphaScreen assay. Using X-ray crystallography, we analyzed structures of the PA-Nter in complex with luteolin at 2.0 angstrom resolution and quambalarine B at 2.5 angstrom resolution, which clearly revealed the binding pose of these polyols coordinated to two manganese ions in the endonuclease active site. Using two distinct assays along with the structural work, we have presumably identified and characterized the molecular mode-of-action of flavonoids in influenza-infected cells. (c) 2020 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2021 Elektronická adresa https://www.sciencedirect.com/science/article/pii/S0223523420307261?via%3Dihub
Počet záznamů: 1