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Retinazone inhibits certain blood-borne human viruses including Ebola virus Zaire

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dc.contributor.authorKesel, A.J.
dc.contributor.authorHuang, Z.
dc.contributor.authorMurray, M.G.
dc.contributor.authorPrichard, M.N.
dc.contributor.authorCaboni, L.
dc.contributor.authorNevin, D.K.
dc.contributor.authorFayne, D.
dc.contributor.authorLloyd, D.G.
dc.contributor.authorDetorio, M.A.
dc.contributor.authorSchinazi, R.F.
dc.date.issued2014
dc.descriptionData source: Supplementary material, https://www.intmedpress.com/uploads/documents/0089_Kesel_Additional_file1.pdf Link to a related website: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714485, Open Access via Unpaywall
dc.description.abstractBackground: Human HBV and HIV integrate their retro-transcribed DNA proviruses into the human host genome. Existing antiretroviral drug regimens fail to directly target these intrachromosomal xenogenomes, leading to persistence of viral genetic information. Retinazone (RTZ) constitutes a novel vitamin A-derived (retinoid) thiosemicarbazone derivative with broad-spectrum antiviral activity versus HIV, HCV, varicella-zoster virus and cytomegalovirus. Methods: The in vitro inhibitory action of RTZ on HIV-1 strain LAI, human HBV strain ayw, HCV-1b strain Con1, enhanced green fluorescent protein-expressing Ebola virus Zaire 1976 strain Mayinga, wild-type Ebola virus Zaire 1976 strain Mayinga, human herpesvirus 6B and Kaposi's sarcoma-associated herpesvirus replication was investigated. The binding of RTZ to human glucocorticoid receptor was determined. Results: RTZ inhibits blood-borne human HBV multiplication in vitro by covalent inactivation of intragenic and intraexonic viral glucocorticoid response elements, and, in close analogy, RTZ suppresses HIV-1 multiplication in vitro. RTZ disrupts the multiplication of blood-borne human HCV and Ebola Zaire virus at nanomolar concentrations in vitro. RTZ has the capacity to bind to human glucocorticoid receptor, to selectively and covalently bind to intraexonic viral glucocorticoid response elements, and thereby to inactivate human genome-integrated proviral DNA of human HBV and HIV. Conclusions: RTZ represents the first reported antiviral agent capable of eradicating HIV and HBV proviruses from their human host. Furthermore, RTZ represents a potent and efficacious small-molecule in vitro inhibitor of Ebola virus Zaire 1976 strain Mayinga replication.
dc.identifier.citationAntiviral Chemistry and Chemotherapy, 2014; 23(5):197-215
dc.identifier.doi10.3851/IMP2568
dc.identifier.issn2040-2066
dc.identifier.issn2040-2066
dc.identifier.urihttps://hdl.handle.net/1959.8/156913
dc.language.isoen
dc.publisherInternational Medical Press
dc.relation.fundingNIH VFAR 2P30–AI–50409
dc.relation.fundingDMID, NIAID, NIH HHSN272201100012I
dc.relation.fundingIrishHigher Education Authority’s Programme for Researchin Third Level Institutions (PRTLI)
dc.relation.fundingIrish Research Council
dc.relation.fundingDell Ireland
dc.relation.fundingHealth Research Board HRB/2007/2
dc.rightsCopyright 2014 International Medical Press
dc.source.urihttps://doi.org/10.3851/IMP2568
dc.subjectimmunodeficiency
dc.subjectherpesvirus
dc.subjectretinazone
dc.titleRetinazone inhibits certain blood-borne human viruses including Ebola virus Zaire
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9915910300901831

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