A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro

Autores
Kaptein, Suzanne J; De Burghgraeve, Tine; Froeyen, Mathy; Pastorino, Boris; Alen, Marijke M. F.; Mondotte, Juan Alberto; Herdewijn, Piet; Jacobs, Michael; de Lamballerie, Xavier; Schols, Dominique; Gamarnik, Andrea Vanesa; Sztaricskai, Ferenc; Neyts, Johan
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Kaptein, Suzanne J. Rega Institute; Bélgica
Fil: De Burghgraeve, Tine . Rega Institute; Bélgica
Fil: Froeyen, Mathy . Rega Institute; Bélgica
Fil: Pastorino, Boris . Université de la Méditerranée. Unité des Virus Emergents; Francia
Fil: Alen, Marijke M. F.. Rega Institute; Bélgica
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
Fil: Herdewijn, Piet. Rega Institute; Bélgica
Fil: Jacobs, Michael. University College London Medical School. Department of Infection; Reino Unido
Fil: de Lamballerie, Xavier. Université de la Méditerranée. Unité des Virus Emergents; Francia
Fil: Schols, Dominique. Rega Institute; Bélgica
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
Fil: Sztaricskai, Ferenc. University of Debrecen. Department of Pharmaceutical Chemistry; Hungría
Fil: Neyts, Johan. Rega Institute; Bélgica
Materia
Dengue Virus
Antivirals
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/12783
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/12783
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitroKaptein, Suzanne JDe Burghgraeve, Tine Froeyen, Mathy Pastorino, Boris Alen, Marijke M. F.Mondotte, Juan AlbertoHerdewijn, PietJacobs, Michaelde Lamballerie, XavierSchols, DominiqueGamarnik, Andrea VanesaSztaricskai, FerencNeyts, JohanDengue VirusAntiviralshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1A 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.Fil: Kaptein, Suzanne J. Rega Institute; BélgicaFil: De Burghgraeve, Tine . Rega Institute; BélgicaFil: Froeyen, Mathy . Rega Institute; BélgicaFil: Pastorino, Boris . Université de la Méditerranée. Unité des Virus Emergents; FranciaFil: Alen, Marijke M. F.. Rega Institute; BélgicaFil: 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; ArgentinaFil: Herdewijn, Piet. Rega Institute; BélgicaFil: Jacobs, Michael. University College London Medical School. Department of Infection; Reino UnidoFil: de Lamballerie, Xavier. Université de la Méditerranée. Unité des Virus Emergents; FranciaFil: Schols, Dominique. Rega Institute; BélgicaFil: 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; ArgentinaFil: Sztaricskai, Ferenc. University of Debrecen. Department of Pharmaceutical Chemistry; HungríaFil: Neyts, Johan. Rega Institute; BélgicaAmerican Society For Microbiology2010-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/12783Kaptein, 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; 5269-52800066-4804enginfo:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/54/12/5269.longinfo:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.00686-10info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:50:14Zoai:ri.conicet.gov.ar:11336/12783instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:50:14.867CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
title A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
spellingShingle A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
Kaptein, Suzanne J
Dengue Virus
Antivirals
title_short A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
title_full A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
title_fullStr A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
title_full_unstemmed A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
title_sort A derivate of the antibiotic doxorubicin is a selective inhibitor of dengue and yellow fever virus replication in vitro
dc.creator.none.fl_str_mv Kaptein, Suzanne J
De Burghgraeve, Tine
Froeyen, Mathy
Pastorino, Boris
Alen, Marijke M. F.
Mondotte, Juan Alberto
Herdewijn, Piet
Jacobs, Michael
de Lamballerie, Xavier
Schols, Dominique
Gamarnik, Andrea Vanesa
Sztaricskai, Ferenc
Neyts, Johan
author Kaptein, Suzanne J
author_facet Kaptein, Suzanne J
De Burghgraeve, Tine
Froeyen, Mathy
Pastorino, Boris
Alen, Marijke M. F.
Mondotte, Juan Alberto
Herdewijn, Piet
Jacobs, Michael
de Lamballerie, Xavier
Schols, Dominique
Gamarnik, Andrea Vanesa
Sztaricskai, Ferenc
Neyts, Johan
author_role author
author2 De Burghgraeve, Tine
Froeyen, Mathy
Pastorino, Boris
Alen, Marijke M. F.
Mondotte, Juan Alberto
Herdewijn, Piet
Jacobs, Michael
de Lamballerie, Xavier
Schols, Dominique
Gamarnik, Andrea Vanesa
Sztaricskai, Ferenc
Neyts, Johan
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Dengue Virus
Antivirals
topic Dengue Virus
Antivirals
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Kaptein, Suzanne J. Rega Institute; Bélgica
Fil: De Burghgraeve, Tine . Rega Institute; Bélgica
Fil: Froeyen, Mathy . Rega Institute; Bélgica
Fil: Pastorino, Boris . Université de la Méditerranée. Unité des Virus Emergents; Francia
Fil: Alen, Marijke M. F.. Rega Institute; Bélgica
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
Fil: Herdewijn, Piet. Rega Institute; Bélgica
Fil: Jacobs, Michael. University College London Medical School. Department of Infection; Reino Unido
Fil: de Lamballerie, Xavier. Université de la Méditerranée. Unité des Virus Emergents; Francia
Fil: Schols, Dominique. Rega Institute; Bélgica
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
Fil: Sztaricskai, Ferenc. University of Debrecen. Department of Pharmaceutical Chemistry; Hungría
Fil: Neyts, Johan. Rega Institute; Bélgica
description 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.
publishDate 2010
dc.date.none.fl_str_mv 2010-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/12783
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
0066-4804
url http://hdl.handle.net/11336/12783
identifier_str_mv 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
0066-4804
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://aac.asm.org/content/54/12/5269.long
info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.00686-10
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society For Microbiology
publisher.none.fl_str_mv American Society For Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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