Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses

Autores
Quintana, Verónica Mara; Selisko, B.; Brunetti, Jesús Emanuel; Eydoux, C.; Guillemot, J.C.; Canard, B.; Damonte, Elsa Beatriz; Julander, J.; Castilla, Viviana
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Flaviviruses constitute a public health concern because of their global burden and the lack of specific antiviral treatment. Here we investigated the antiviral activity of the alkaloid anisomycin against dengue (DENV) and Zika (ZIKV) viruses. At non-cytotoxic concentrations, anisomycin strongly inhibited the replication of reference strains and clinical isolates of all DENV serotypes and Asian and African strains of ZIKV in Vero cells. Anisomycin also prevented DENV and ZIKV multiplication in human cell lines. While initial steps of DENV and ZIKV replicative cycle were unaffected, a high inhibition of viral protein expression was demonstrated after treatment with anisomycin. DENV RNA synthesis was strongly reduced in anisomycin treated cultures, but the compounddid not exert a direct inhibitory effect on 2′ O-methyltransferase or RNA polymerase activities of DENV NS5 protein. Furthermore, anisomycin-mediated activation of p38 signaling was not related to the antiviral action ofthe compound. The evaluation of anisomycin efficacy in a mouse model of ZIKV morbidity and mortality revealed that animals treated with a low dose of anisomycin exhibited a significant reduction in viremia levels anddied significantly later than the control group. This protective effect was lost at higher doses, though. In conclusion, anisomycin is a potent and selective in vitro inhibitor of DENV and ZIKV that impairs a post-entry step of viral replication; and a low-dose anisomycin treatment may provide some minimal benefit in a mouse model.
Fil: Quintana, Verónica Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Selisko, B.. Centre National de la Recherche Scientifique; Francia
Fil: Brunetti, Jesús Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Eydoux, C.. Centre National de la Recherche Scientifique; Francia
Fil: Guillemot, J.C.. Centre National de la Recherche Scientifique; Francia
Fil: Canard, B.. Centre National de la Recherche Scientifique; Francia
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Julander, J.. State University of Utah; Estados Unidos
Fil: Castilla, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
FLAVIVIRUS
DENGUE
ZIKA
ANISOMYCIN
ANTIVIRAL
P38
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:11336/144172
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antiviral activity of the natural alkaloid anisomycin against dengue and Zika virusesQuintana, Verónica MaraSelisko, B.Brunetti, Jesús EmanuelEydoux, C.Guillemot, J.C.Canard, B.Damonte, Elsa BeatrizJulander, J.Castilla, VivianaFLAVIVIRUSDENGUEZIKAANISOMYCINANTIVIRALP38https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Flaviviruses constitute a public health concern because of their global burden and the lack of specific antiviral treatment. Here we investigated the antiviral activity of the alkaloid anisomycin against dengue (DENV) and Zika (ZIKV) viruses. At non-cytotoxic concentrations, anisomycin strongly inhibited the replication of reference strains and clinical isolates of all DENV serotypes and Asian and African strains of ZIKV in Vero cells. Anisomycin also prevented DENV and ZIKV multiplication in human cell lines. While initial steps of DENV and ZIKV replicative cycle were unaffected, a high inhibition of viral protein expression was demonstrated after treatment with anisomycin. DENV RNA synthesis was strongly reduced in anisomycin treated cultures, but the compounddid not exert a direct inhibitory effect on 2′ O-methyltransferase or RNA polymerase activities of DENV NS5 protein. Furthermore, anisomycin-mediated activation of p38 signaling was not related to the antiviral action ofthe compound. The evaluation of anisomycin efficacy in a mouse model of ZIKV morbidity and mortality revealed that animals treated with a low dose of anisomycin exhibited a significant reduction in viremia levels anddied significantly later than the control group. This protective effect was lost at higher doses, though. In conclusion, anisomycin is a potent and selective in vitro inhibitor of DENV and ZIKV that impairs a post-entry step of viral replication; and a low-dose anisomycin treatment may provide some minimal benefit in a mouse model.Fil: Quintana, Verónica Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Selisko, B.. Centre National de la Recherche Scientifique; FranciaFil: Brunetti, Jesús Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Eydoux, C.. Centre National de la Recherche Scientifique; FranciaFil: Guillemot, J.C.. Centre National de la Recherche Scientifique; FranciaFil: Canard, B.. Centre National de la Recherche Scientifique; FranciaFil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Julander, J.. State University of Utah; Estados UnidosFil: Castilla, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaElsevier Science2020-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/144172Quintana, Verónica Mara; Selisko, B.; Brunetti, Jesús Emanuel; Eydoux, C.; Guillemot, J.C.; et al.; Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses; Elsevier Science; Antiviral Research; 4-2020; 1-100166-3542CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0166354219304619info:eu-repo/semantics/altIdentifier/doi/10.1016/j.antiviral.2020.104749info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:56Zoai:ri.conicet.gov.ar:11336/144172instacron: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:34982025-09-03 10:04:57.197CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses
title Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses
spellingShingle Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses
Quintana, Verónica Mara
FLAVIVIRUS
DENGUE
ZIKA
ANISOMYCIN
ANTIVIRAL
P38
title_short Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses
title_full Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses
title_fullStr Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses
title_full_unstemmed Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses
title_sort Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses
dc.creator.none.fl_str_mv Quintana, Verónica Mara
Selisko, B.
Brunetti, Jesús Emanuel
Eydoux, C.
Guillemot, J.C.
Canard, B.
Damonte, Elsa Beatriz
Julander, J.
Castilla, Viviana
author Quintana, Verónica Mara
author_facet Quintana, Verónica Mara
Selisko, B.
Brunetti, Jesús Emanuel
Eydoux, C.
Guillemot, J.C.
Canard, B.
Damonte, Elsa Beatriz
Julander, J.
Castilla, Viviana
author_role author
author2 Selisko, B.
Brunetti, Jesús Emanuel
Eydoux, C.
Guillemot, J.C.
Canard, B.
Damonte, Elsa Beatriz
Julander, J.
Castilla, Viviana
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv FLAVIVIRUS
DENGUE
ZIKA
ANISOMYCIN
ANTIVIRAL
P38
topic FLAVIVIRUS
DENGUE
ZIKA
ANISOMYCIN
ANTIVIRAL
P38
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Flaviviruses constitute a public health concern because of their global burden and the lack of specific antiviral treatment. Here we investigated the antiviral activity of the alkaloid anisomycin against dengue (DENV) and Zika (ZIKV) viruses. At non-cytotoxic concentrations, anisomycin strongly inhibited the replication of reference strains and clinical isolates of all DENV serotypes and Asian and African strains of ZIKV in Vero cells. Anisomycin also prevented DENV and ZIKV multiplication in human cell lines. While initial steps of DENV and ZIKV replicative cycle were unaffected, a high inhibition of viral protein expression was demonstrated after treatment with anisomycin. DENV RNA synthesis was strongly reduced in anisomycin treated cultures, but the compounddid not exert a direct inhibitory effect on 2′ O-methyltransferase or RNA polymerase activities of DENV NS5 protein. Furthermore, anisomycin-mediated activation of p38 signaling was not related to the antiviral action ofthe compound. The evaluation of anisomycin efficacy in a mouse model of ZIKV morbidity and mortality revealed that animals treated with a low dose of anisomycin exhibited a significant reduction in viremia levels anddied significantly later than the control group. This protective effect was lost at higher doses, though. In conclusion, anisomycin is a potent and selective in vitro inhibitor of DENV and ZIKV that impairs a post-entry step of viral replication; and a low-dose anisomycin treatment may provide some minimal benefit in a mouse model.
Fil: Quintana, Verónica Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Selisko, B.. Centre National de la Recherche Scientifique; Francia
Fil: Brunetti, Jesús Emanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Eydoux, C.. Centre National de la Recherche Scientifique; Francia
Fil: Guillemot, J.C.. Centre National de la Recherche Scientifique; Francia
Fil: Canard, B.. Centre National de la Recherche Scientifique; Francia
Fil: Damonte, Elsa Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Julander, J.. State University of Utah; Estados Unidos
Fil: Castilla, Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
description Flaviviruses constitute a public health concern because of their global burden and the lack of specific antiviral treatment. Here we investigated the antiviral activity of the alkaloid anisomycin against dengue (DENV) and Zika (ZIKV) viruses. At non-cytotoxic concentrations, anisomycin strongly inhibited the replication of reference strains and clinical isolates of all DENV serotypes and Asian and African strains of ZIKV in Vero cells. Anisomycin also prevented DENV and ZIKV multiplication in human cell lines. While initial steps of DENV and ZIKV replicative cycle were unaffected, a high inhibition of viral protein expression was demonstrated after treatment with anisomycin. DENV RNA synthesis was strongly reduced in anisomycin treated cultures, but the compounddid not exert a direct inhibitory effect on 2′ O-methyltransferase or RNA polymerase activities of DENV NS5 protein. Furthermore, anisomycin-mediated activation of p38 signaling was not related to the antiviral action ofthe compound. The evaluation of anisomycin efficacy in a mouse model of ZIKV morbidity and mortality revealed that animals treated with a low dose of anisomycin exhibited a significant reduction in viremia levels anddied significantly later than the control group. This protective effect was lost at higher doses, though. In conclusion, anisomycin is a potent and selective in vitro inhibitor of DENV and ZIKV that impairs a post-entry step of viral replication; and a low-dose anisomycin treatment may provide some minimal benefit in a mouse model.
publishDate 2020
dc.date.none.fl_str_mv 2020-04
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/11336/144172
Quintana, Verónica Mara; Selisko, B.; Brunetti, Jesús Emanuel; Eydoux, C.; Guillemot, J.C.; et al.; Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses; Elsevier Science; Antiviral Research; 4-2020; 1-10
0166-3542
CONICET Digital
CONICET
url http://hdl.handle.net/11336/144172
identifier_str_mv Quintana, Verónica Mara; Selisko, B.; Brunetti, Jesús Emanuel; Eydoux, C.; Guillemot, J.C.; et al.; Antiviral activity of the natural alkaloid anisomycin against dengue and Zika viruses; Elsevier Science; Antiviral Research; 4-2020; 1-10
0166-3542
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0166354219304619
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.antiviral.2020.104749
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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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