Structure-activity relationships of fluorene compounds inhibiting HCV variants.
Antiviral Agents
/ chemistry
Fluorenes
/ chemistry
Genetic Variation
Hepacivirus
/ drug effects
Hepatitis C
/ drug therapy
Humans
Intracellular Signaling Peptides and Proteins
/ antagonists & inhibitors
Molecular Docking Simulation
Structure-Activity Relationship
Viral Nonstructural Proteins
/ antagonists & inhibitors
Direct-acting antiviral agent (DAA)
Hepatitis c virus
Molecular docking
NS5A inhibitor
Resistance-associated variant (RAV)
Structure-activity relationship (SAR)
Journal
Antiviral research
ISSN: 1872-9096
Titre abrégé: Antiviral Res
Pays: Netherlands
ID NLM: 8109699
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
15
10
2019
revised:
04
12
2019
accepted:
09
12
2019
pubmed:
22
12
2019
medline:
1
12
2020
entrez:
22
12
2019
Statut:
ppublish
Résumé
Approximately 71 million people suffer from hepatitis C virus (HCV) infection worldwide. Persistent HCV infection causes liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, resulting in approximately 400,000 deaths annually. Effective direct-acting antiviral agents (DAAs) have been developed and are currently used for HCV treatment targeting the following three proteins: NS3/4A proteinase that cleaves the HCV polyprotein into various functional proteins, RNA-dependent RNA polymerase (designated as NS5B), and NS5A, which is required for the formation of double membrane vesicles serving as RNA replication organelles. At least one compound inhibiting NS5A is included in current HCV treatment regimens due to the high efficacy and low toxicity of drugs targeting NS5A. Here we report fluorene compounds showing strong inhibitory effects on GT 1b and 3a of HCV. Moreover, some compounds were effective against resistance-associated variants to DAAs. The structure-activity relationships of the compounds were analyzed. Furthermore, we investigated the molecular bases of the inhibitory activities of some compounds by the molecular docking method.
Identifiants
pubmed: 31862501
pii: S0166-3542(19)30579-0
doi: 10.1016/j.antiviral.2019.104678
pii:
doi:
Substances chimiques
Antiviral Agents
0
Fluorenes
0
Intracellular Signaling Peptides and Proteins
0
NS3 protein, hepatitis C virus
0
NS4A cofactor peptide, Hepatitis C virus
0
Viral Nonstructural Proteins
0
NS-5 protein, hepatitis C virus
EC 2.7.7.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104678Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.