Discovery of novel West Nile Virus protease inhibitor based on isobenzonafuranone and triazolic derivatives of eugenol and indan-1,3-dione scaffolds.
Antiviral Agents
/ chemistry
Catalytic Domain
/ drug effects
Drug Discovery
Endopeptidases
/ chemistry
Eugenol
/ chemistry
Histidine
/ chemistry
Indans
/ chemistry
Inhibitory Concentration 50
Molecular Docking Simulation
Protease Inhibitors
/ chemistry
Serine
/ chemistry
Structure-Activity Relationship
Viral Nonstructural Proteins
/ antagonists & inhibitors
West Nile virus
/ enzymology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
12
04
2019
accepted:
11
09
2019
entrez:
27
9
2019
pubmed:
27
9
2019
medline:
13
3
2020
Statut:
epublish
Résumé
The West Nile Virus (WNV) NS2B-NS3 protease is an attractive target for the development of therapeutics against this arboviral pathogen. In the present investigation, the screening of a small library of fifty-eight synthetic compounds against the NS2-NB3 protease of WNV is described. The following groups of compounds were evaluated: 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones; eugenol derivatives bearing 1,2,3-triazolic functionalities; and indan-1,3-diones with 1,2,3-triazolic functionalities. The most promising of these was a eugenol derivative, namely 4-(3-(4-allyl-2-methoxyphenoxy)-propyl)-1-(2-bromobenzyl)-1H-1,2,3-triazole (35), which inhibited the protease with IC50 of 6.86 μmol L-1. Enzyme kinetic assays showed that this derivative of eugenol presents competitive inhibition behaviour. Molecular docking calculations predicted a recognition pattern involving the residues His51 and Ser135, which are members of the catalytic triad of the WNV NS2B-NS3 protease.
Identifiants
pubmed: 31557229
doi: 10.1371/journal.pone.0223017
pii: PONE-D-19-08554
pmc: PMC6762200
doi:
Substances chimiques
Antiviral Agents
0
Indans
0
Protease Inhibitors
0
Viral Nonstructural Proteins
0
Eugenol
3T8H1794QW
Serine
452VLY9402
Histidine
4QD397987E
Endopeptidases
EC 3.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0223017Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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