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dc.contributor.author
Kaptein, Suzanne J
dc.contributor.author
De Burghgraeve, Tine
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Froeyen, Mathy
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Pastorino, Boris
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Alen, Marijke M. F.
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Mondotte, Juan Alberto
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Herdewijn, Piet
dc.contributor.author
Jacobs, Michael
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de Lamballerie, Xavier
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Schols, Dominique
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Gamarnik, Andrea Vanesa
dc.contributor.author
Sztaricskai, Ferenc
dc.contributor.author
Neyts, Johan
dc.date.available
2017-02-08T21:55:22Z
dc.date.issued
2010-12
dc.identifier.citation
Kaptein, Suzanne J; De Burghgraeve, Tine ; Froeyen, Mathy ; Pastorino, Boris ; Alen, Marijke M. F.; et al.; A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro; American Society For Microbiology; Antimicrobial Agents And Chemotherapy; 54; 12; 12-2010; 5269-5280
dc.identifier.issn
0066-4804
dc.identifier.uri
http://hdl.handle.net/11336/12783
dc.description.abstract
A doxorubicin derivate, SA-17, that carries a squaric acid amide ester moiety at the carbohydrate (α-l-daunosaminyl) group was identified as a selective inhibitor of in vitro dengue virus (DENV) serotype 2 replication (50% effective concentration [EC(50)] = 0.34 ± 0.20 μg/ml [0.52 ± 0.31 μM]). SA-17 is markedly less cytostatic than the parent compound, resulting in a selectivity index value of ∼100. SA-17 also inhibits yellow fever virus 17D (YFV-17D) replication (EC(50) = 3.1 ± 1.0 μg/ml [4.8 ± 1.5 μM]), although less efficiently than DENV replication, but proved inactive against a variety of enveloped and nonenveloped viruses. SA-17 inhibits in vitro flavivirus replication in a dose-dependent manner, as was assessed by virus yield reduction assays and quantification of viral RNA by means of real-time quantitative reverse transcriptase PCR (RT-qPCR) (∼2 to 3 log reduction). The anti-DENV activity was confirmed using a Renilla luciferase-expressing dengue reporter virus. Time-of-drug-addition studies revealed that SA-17 acts at the very early stages of the viral replication cycle (i.e., virus attachment and/or virus entry). This observation was corroborated by the observation that SA-17, unlike the nucleoside analogue ribavirin, does not inhibit the replication of DENV subgenomic replicons. Preincubation of high-titer stocks of DENV or YFV-17D with ≥5 μg/ml SA-17 resulted in 100% inhibition of viral infectivity (≥3 log reduction). SA-17, however, did not prove virucidal.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Society For Microbiology
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Dengue Virus
dc.subject
Antivirals
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Virología
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-02-07T13:52:59Z
dc.journal.volume
54
dc.journal.number
12
dc.journal.pagination
5269-5280
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington DC
dc.description.fil
Fil: Kaptein, Suzanne J. Rega Institute; Bélgica
dc.description.fil
Fil: De Burghgraeve, Tine . Rega Institute; Bélgica
dc.description.fil
Fil: Froeyen, Mathy . Rega Institute; Bélgica
dc.description.fil
Fil: Pastorino, Boris . Université de la Méditerranée. Unité des Virus Emergents; Francia
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Fil: Alen, Marijke M. F.. Rega Institute; Bélgica
dc.description.fil
Fil: Mondotte, Juan Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
dc.description.fil
Fil: Herdewijn, Piet. Rega Institute; Bélgica
dc.description.fil
Fil: Jacobs, Michael. University College London Medical School. Department of Infection; Reino Unido
dc.description.fil
Fil: de Lamballerie, Xavier. Université de la Méditerranée. Unité des Virus Emergents; Francia
dc.description.fil
Fil: Schols, Dominique. Rega Institute; Bélgica
dc.description.fil
Fil: Gamarnik, Andrea Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquimicas de Buenos Aires; Argentina. Fundación Instituto Leloir; Argentina
dc.description.fil
Fil: Sztaricskai, Ferenc. University of Debrecen. Department of Pharmaceutical Chemistry; Hungría
dc.description.fil
Fil: Neyts, Johan. Rega Institute; Bélgica
dc.journal.title
Antimicrobial Agents And Chemotherapy
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/54/12/5269.long
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1128/AAC.00686-10
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