Hepatitis C virus in vitro replication is efficiently inhibited by acridone Fac4

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dc.contributor.authorCampos, Guilherme Rodrigues Fernandes [UNESP]
dc.contributor.authorBittar, Cíntia [UNESP]
dc.contributor.authorJardim, Ana Carolina Gomes
dc.contributor.authorShimizu, Jacqueline Farinha [UNESP]
dc.contributor.authorBatista, Mariana Nogueira [UNESP]
dc.contributor.authorPaganini, Eder Ramos [UNESP]
dc.contributor.authorde Assis, Letícia Ribeiro [UNESP]
dc.contributor.authorBartlett, Christopher
dc.contributor.authorHarris, Mark
dc.contributor.authorBolzani, Vanderlan da Silva [UNESP]
dc.contributor.authorRegasini, Luis Octavio [UNESP]
dc.contributor.authorRahal, Paula [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal de Uberlândia (UFU)
dc.contributor.institutionUniversity of Leeds
dc.date.accessioned2018-12-11T17:33:26Z
dc.date.available2018-12-11T17:33:26Z
dc.date.issued2017-07-01
dc.description.abstractHepatitis 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 harbouring the HCV genotype 2a subgenomic replicon SGR-Feo-JFH-1. Cells were incubated in the presence or absence of compounds for 72 h and cell viability and replication levels were assessed by MTT and luciferase assays, respectively. At a concentration of 5 μM the acridone Fac4 exhibited a >90%inhibition of HCV replication with no effect on 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 JFH-1 replication to approximately 70 %, while no effect was observed on virus entry. The antiviral activity of Fac4 was also observed on viral release, with almost 80% of inhibition. No inhibitory effect was observed against genotype 3 replication. Fac4 was able to intercalate into dsRNA, however did not inhibit NS5B polymerase activity or translation driven by the HCV IRES. Although its mode of action is partly understood, Fac4 presents significant inhibition of HCV replication and can therefore be considered as a candidate for the development of a future anti-HCV treatment.en
dc.description.affiliationInstitute of Bioscience Language and Exact Science IBILCE UNESP –São Paulo State University
dc.description.affiliationInstitute of Biomedical Science ICBIM UFU –Federal University of Uberlândia
dc.description.affiliationSchool of Molecular and Cellular Biology Faculty of Biological Sciences Astbury Centre for Structural Molecular Biology University of Leeds
dc.description.affiliationInstitute of Chemistry São Paulo State University
dc.description.affiliationUnespInstitute of Bioscience Language and Exact Science IBILCE UNESP –São Paulo State University
dc.description.affiliationUnespInstitute of Chemistry São Paulo State University
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorshipIdCNPq: 165802/2015-4
dc.description.sponsorshipIdFAPESP: 2012/01403-9
dc.description.sponsorshipIdFAPESP: 2014/22198-0
dc.description.sponsorshipIdCNPq: 445021/2014-4
dc.description.sponsorshipIdFAPEMIG: APQ-00587-14
dc.description.sponsorshipIdCNPq: SICONV 793988/2013
dc.format.extent1693-1701
dc.identifierhttp://dx.doi.org/10.1099/jgv.0.000808
dc.identifier.citationJournal of General Virology, v. 98, n. 7, p. 1693-1701, 2017.
dc.identifier.doi10.1099/jgv.0.000808
dc.identifier.file2-s2.0-85026634064.pdf
dc.identifier.issn1465-2099
dc.identifier.issn0022-1317
dc.identifier.lattes7991082362671212
dc.identifier.orcid0000-0001-5693-6148
dc.identifier.scopus2-s2.0-85026634064
dc.identifier.urihttp://hdl.handle.net/11449/179069
dc.language.isoeng
dc.relation.ispartofJournal of General Virology
dc.relation.ispartofsjr1,325
dc.relation.ispartofsjr1,325
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectAcridones
dc.subjectAntivirals
dc.subjectHCV
dc.subjectInhibition of viral replication
dc.subjectTreatment
dc.titleHepatitis C virus in vitro replication is efficiently inhibited by acridone Fac4en
dc.typeArtigo
unesp.author.lattes7991082362671212[12]
unesp.author.orcid0000-0001-5693-6148[12]

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