Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors.
Antiviral Agents
/ chemistry
Crystallography, X-Ray
Drug Evaluation, Preclinical
Endonucleases
/ antagonists & inhibitors
Enzyme Assays
/ methods
Enzyme Inhibitors
/ chemistry
Flavonoids
/ chemistry
Influenza A virus
/ enzymology
Microbial Sensitivity Tests
Molecular Structure
Protein Binding
Protein Domains
RNA-Dependent RNA Polymerase
/ antagonists & inhibitors
Structure-Activity Relationship
Viral Proteins
/ antagonists & inhibitors
Influenza
Neuraminidase
PA(N) endonuclease Inhibitors
Polyphenols
RNA polymerase
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 Dec 2020
15 Dec 2020
Historique:
received:
22
06
2020
revised:
20
07
2020
accepted:
09
08
2020
pubmed:
5
9
2020
medline:
27
5
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
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 IC
Identifiants
pubmed: 32883638
pii: S0223-5234(20)30726-1
doi: 10.1016/j.ejmech.2020.112754
pii:
doi:
Substances chimiques
Antiviral Agents
0
Enzyme Inhibitors
0
Flavonoids
0
Viral Proteins
0
RNA-Dependent RNA Polymerase
EC 2.7.7.48
Endonucleases
EC 3.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112754Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interest or personal relationship that could have appeared to influence the work reported in the paper.