Campos, GRF, Bittar, C, Jardim, ACG et al. (9 more authors) (2017) Hepatitis C virus in vitro replication is efficiently inhibited by acridone Fac4. Journal of General Virology, 98 (7). pp. 1693-1701. ISSN 0022-1317
Abstract
Hepatitis C Virus (HCV) affects about 170 million people worldwide. The current treatment has a high cost and variable response rates according to the virus genotype. Acridones, a group of compounds extracted from natural sources, showed potential antiviral actions against HCV. Thus, this study aimed to evaluate the effect of a panel of 14 synthetic acridones on the HCV life cycle. The compounds were screened using an Huh7.5 cell line stably harboring the HCV genotype 2a subgenomic replicon SGR-JFH1-FEO. Cells were incubated in the presence or absence of compounds for 72 hours and cell viability and replication levels were assessed by MTT and luciferase assays, respectively. The acridone Fac4 at 5 μM inhibited approximately 90% of HCV replication with 100 % of cell viability. The effects of Fac4 on virus replication, entry and release steps were evaluated in Huh7.5 cells infected with the JFH-1 isolate of HCV (HCVcc). Fac4 inhibited approximately 70 % of JFH-1 replication, while no effect was observed on virus entry. The antiviral activity of Fac4 was also observed on the viral release, with almost 80% of inhibition. No inhibitory effect was observed against genotype 3 replication. Fac4 demonstrated 40% of intercalation into dsRNA, however did not inhibit T7 polymerase activity, as well as translation by IRES interaction. Although its mode of action is partly understood, the Fac4 presents significant inhibition of Hepatitis C virus replication and can therefore be considered as a candidate for the development of a future anti-HCV treatment.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016, the Author(s). This is an author produced version of a paper published in Journal of General Virology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | antivirals; HCV; acridones; inhibition of viral replication; treatment. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Virology 1 (Leeds) |
Funding Information: | Funder Grant number Wellcome Trust 096670/Z/11/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Jul 2017 10:42 |
Last Modified: | 12 Jul 2018 00:38 |
Status: | Published |
Publisher: | Microbiology Society |
Identification Number: | 10.1099/jgv.0.000808 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:119500 |