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Khaya grandifoliola C.DC: a potential source of active ingredients against hepatitis C virus in vitro

In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on the hepatitis C virus (HCV) life cycle in vitro and identified some of the chemical constituents contained in the fraction with the most antiviral activity. Dried bark powder was extracted by maceration in...

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Published in:Archives of virology 2016-05, Vol.161 (5), p.1169-1181
Main Authors: Galani, Borris Rosnay Tietcheu, Sahuc, Marie-Emmanuelle, Sass, Gabriele, Njayou, Frédéric Nico, Loscher, Christine, Mkounga, Pierre, Deloison, Gaspard, Brodin, Priscille, Rouillé, Yves, Tiegs, Gisa, Séron, Karin, Moundipa, Paul Fewou
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cited_by cdi_FETCH-LOGICAL-c439t-e495200aac1433fce5883be441873ceaa658ff84040e8b48fdc619fd9dca830d3
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creator Galani, Borris Rosnay Tietcheu
Sahuc, Marie-Emmanuelle
Sass, Gabriele
Njayou, Frédéric Nico
Loscher, Christine
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Brodin, Priscille
Rouillé, Yves
Tiegs, Gisa
Séron, Karin
Moundipa, Paul Fewou
description In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on the hepatitis C virus (HCV) life cycle in vitro and identified some of the chemical constituents contained in the fraction with the most antiviral activity. Dried bark powder was extracted by maceration in a methylene chloride/methanol (MCM) system (50:50; v/v) and separated on silica gel by flash chromatography. Infection and replication rates in Huh-7 cells were investigated by luciferase reporter assay and indirect immunofluorescence assay using subgenomic replicons, HCV pseudotyped particles, and cell-culture-derived HCV (HCVcc), respectively. Cell viability was assessed by MTT assay, and cellular gene expression was analysed by qRT-PCR. The chemical composition of the fraction with the most antiviral activity was analysed by coupled gas chromatography and mass spectrometry (GC-MS). Five fractions of different polarities (F0-F100) were obtained from the MCM extract. One fraction (KgF25) showed the strongest antiviral effect on LucUbiNeoET replicons at nontoxic concentrations. Tested at 100 µg/mL, KgF25 had a high inhibitory effect on HCV replication, comparable to that of 0.01 µM daclatasvir or 1 µM telaprevir. This fraction also inhibited HCVcc infection by mostly targeting the entry step. KgF25 inhibited HCV entry in a pan-genotypic manner by directly inactivating free viral particles. Its antiviral effects were mediated by the transcriptional upregulation of the haem oxygenase-1 gene and interferon antiviral response. Three constituents, namely, benzene, 1,1′-(oxydiethylidene)bis (1), carbamic acid, (4-methylphenyl)-, 1-phenyl (2), and 6-phenyl, 4-(1′-oxyethylphenyl) hexene (3), were identified from the active fraction KgF25 by GC-MS. Khaya grandifoliola contains ingredients capable of acting on different steps of the HCV life cycle.
doi_str_mv 10.1007/s00705-016-2771-5
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identifier ISSN: 0304-8608
ispartof Archives of virology, 2016-05, Vol.161 (5), p.1169-1181
issn 0304-8608
1432-8798
language eng
recordid cdi_hal_primary_oai_HAL_hal_02104486v1
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subjects Antiviral Agents - isolation & purification
Antiviral Agents - pharmacology
Biochemistry
Biomedical and Life Sciences
Biomedicine
Carcinoma, Hepatocellular - metabolism
Cell Line, Tumor
Chromatography
Chromatography, Gel - methods
Cytotoxicity
Dose-Response Relationship, Drug
FDA approval
Fluorescent Antibody Technique
Gas Chromatography-Mass Spectrometry - methods
Hepacivirus - drug effects
Hepatitis C
Hepatitis C virus
Humans
Infections
Infectious Diseases
Khaya
Life Sciences
Liver Neoplasms - metabolism
Mass spectrometry
Medical Microbiology
Meliaceae
Meliaceae - chemistry
Microbiology and Parasitology
Original Article
Plant Bark - chemistry
Plant Extracts - isolation & purification
Plant Extracts - pharmacology
Scientific imaging
Virology
Virus Internalization - drug effects
Virus Replication - drug effects
title Khaya grandifoliola C.DC: a potential source of active ingredients against hepatitis C virus in vitro
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