Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative

Autores
Sepúlveda, Claudia Soledad; García, Cybele C.; Fascio, Mirta Liliana; D'accorso, Norma Beatriz; Docampo Palacios, Maite L.; Pellón, Rolando F.; Damonte, Elsa Beatriz
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
There are no specific approved drugs for the treatment of agents of viral hemorrhagic fevers (HF) and antiviral therapies against these viruses are urgently needed. The present study characterizes the potent and selective antiviral activity against the HF causing arenavirus Junin virus (JUNV) of the compound 10-allyl-6-chloro-4-methoxy-9(10H)-acridone, designated 3f. The effectiveness of 3f to inhibit JUNV multiplication was not importantly affected by the initial multiplicity of infection, with similar effective concentration 50% (EC 50) values in virus yield inhibition assays performed in Vero cells in the range of 0.2-40 plaque forming units (PFU)/cell. Mechanistic studies demonstrated that 3f did not affect the initial steps of adsorption and internalization. The subsequent process of viral RNA synthesis was strongly inhibited, as quantified by real time RT-PCR in compound-treated cells relative to non-treated cells. The addition of exogenous guanosine rescued the infectivity and RNA synthesis of JUNV in 3f-treated cells in a dose-dependent manner, but the reversal was partial, suggesting that the reduction of the GTP pool contributed to the antiviral activity of 3f, but it was not the main operative mechanism. The comparison of 3f with two other viral RNA inhibitors, ribavirin and mycophenolic acid, showed that ribavirin did not act against JUNV through the cellular enzyme inosine monophosphate dehydrogenase (IMPDH) inhibition whereas the anti-JUNV activity of mycophenolic acid was mainly targeted at this enzyme.
Fil: Sepúlveda, Claudia Soledad. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: García, Cybele C.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Fascio, Mirta Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: D'accorso, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Docampo Palacios, Maite L.. Universidad de La Habana; Cuba
Fil: Pellón, Rolando F.. Universidad de La Habana; Cuba
Fil: Damonte, Elsa Beatriz. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
ACRIDONE
ANTIVIRAL
HEMORRHAGIC FEVER VIRUS
INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH)
JUNIN VIRUS
RNA SYNTHESIS
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:11336/114259
Acceder
id CONICETDig_ce32abd5dac4abfa3658e1493f99bcbd
oai_identifier_str oai:ri.conicet.gov.ar:11336/114259
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of Junin virus RNA synthesis by an antiviral acridone derivativeSepúlveda, Claudia SoledadGarcía, Cybele C.Fascio, Mirta LilianaD'accorso, Norma BeatrizDocampo Palacios, Maite L.Pellón, Rolando F.Damonte, Elsa BeatrizACRIDONEANTIVIRALHEMORRHAGIC FEVER VIRUSINOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH)JUNIN VIRUSRNA SYNTHESIShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1There are no specific approved drugs for the treatment of agents of viral hemorrhagic fevers (HF) and antiviral therapies against these viruses are urgently needed. The present study characterizes the potent and selective antiviral activity against the HF causing arenavirus Junin virus (JUNV) of the compound 10-allyl-6-chloro-4-methoxy-9(10H)-acridone, designated 3f. The effectiveness of 3f to inhibit JUNV multiplication was not importantly affected by the initial multiplicity of infection, with similar effective concentration 50% (EC 50) values in virus yield inhibition assays performed in Vero cells in the range of 0.2-40 plaque forming units (PFU)/cell. Mechanistic studies demonstrated that 3f did not affect the initial steps of adsorption and internalization. The subsequent process of viral RNA synthesis was strongly inhibited, as quantified by real time RT-PCR in compound-treated cells relative to non-treated cells. The addition of exogenous guanosine rescued the infectivity and RNA synthesis of JUNV in 3f-treated cells in a dose-dependent manner, but the reversal was partial, suggesting that the reduction of the GTP pool contributed to the antiviral activity of 3f, but it was not the main operative mechanism. The comparison of 3f with two other viral RNA inhibitors, ribavirin and mycophenolic acid, showed that ribavirin did not act against JUNV through the cellular enzyme inosine monophosphate dehydrogenase (IMPDH) inhibition whereas the anti-JUNV activity of mycophenolic acid was mainly targeted at this enzyme.Fil: Sepúlveda, Claudia Soledad. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: García, Cybele C.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Fascio, Mirta Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: D'accorso, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Docampo Palacios, Maite L.. Universidad de La Habana; CubaFil: Pellón, Rolando F.. Universidad de La Habana; CubaFil: Damonte, Elsa Beatriz. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaElsevier Science2012-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/114259Sepúlveda, Claudia Soledad; García, Cybele C.; Fascio, Mirta Liliana; D'accorso, Norma Beatriz; Docampo Palacios, Maite L.; et al.; Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative; Elsevier Science; Antiviral Research; 93; 1; 1-2012; 16-220166-3542CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0166354211004578info:eu-repo/semantics/altIdentifier/doi/10.1016/j.antiviral.2011.10.007info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:15:31Zoai:ri.conicet.gov.ar:11336/114259instacron: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 10:15:32.12CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative
title Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative
spellingShingle Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative
Sepúlveda, Claudia Soledad
ACRIDONE
ANTIVIRAL
HEMORRHAGIC FEVER VIRUS
INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH)
JUNIN VIRUS
RNA SYNTHESIS
title_short Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative
title_full Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative
title_fullStr Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative
title_full_unstemmed Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative
title_sort Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative
dc.creator.none.fl_str_mv Sepúlveda, Claudia Soledad
García, Cybele C.
Fascio, Mirta Liliana
D'accorso, Norma Beatriz
Docampo Palacios, Maite L.
Pellón, Rolando F.
Damonte, Elsa Beatriz
author Sepúlveda, Claudia Soledad
author_facet Sepúlveda, Claudia Soledad
García, Cybele C.
Fascio, Mirta Liliana
D'accorso, Norma Beatriz
Docampo Palacios, Maite L.
Pellón, Rolando F.
Damonte, Elsa Beatriz
author_role author
author2 García, Cybele C.
Fascio, Mirta Liliana
D'accorso, Norma Beatriz
Docampo Palacios, Maite L.
Pellón, Rolando F.
Damonte, Elsa Beatriz
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ACRIDONE
ANTIVIRAL
HEMORRHAGIC FEVER VIRUS
INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH)
JUNIN VIRUS
RNA SYNTHESIS
topic ACRIDONE
ANTIVIRAL
HEMORRHAGIC FEVER VIRUS
INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH)
JUNIN VIRUS
RNA SYNTHESIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv There are no specific approved drugs for the treatment of agents of viral hemorrhagic fevers (HF) and antiviral therapies against these viruses are urgently needed. The present study characterizes the potent and selective antiviral activity against the HF causing arenavirus Junin virus (JUNV) of the compound 10-allyl-6-chloro-4-methoxy-9(10H)-acridone, designated 3f. The effectiveness of 3f to inhibit JUNV multiplication was not importantly affected by the initial multiplicity of infection, with similar effective concentration 50% (EC 50) values in virus yield inhibition assays performed in Vero cells in the range of 0.2-40 plaque forming units (PFU)/cell. Mechanistic studies demonstrated that 3f did not affect the initial steps of adsorption and internalization. The subsequent process of viral RNA synthesis was strongly inhibited, as quantified by real time RT-PCR in compound-treated cells relative to non-treated cells. The addition of exogenous guanosine rescued the infectivity and RNA synthesis of JUNV in 3f-treated cells in a dose-dependent manner, but the reversal was partial, suggesting that the reduction of the GTP pool contributed to the antiviral activity of 3f, but it was not the main operative mechanism. The comparison of 3f with two other viral RNA inhibitors, ribavirin and mycophenolic acid, showed that ribavirin did not act against JUNV through the cellular enzyme inosine monophosphate dehydrogenase (IMPDH) inhibition whereas the anti-JUNV activity of mycophenolic acid was mainly targeted at this enzyme.
Fil: Sepúlveda, Claudia Soledad. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: García, Cybele C.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina
Fil: Fascio, Mirta Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: D'accorso, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Docampo Palacios, Maite L.. Universidad de La Habana; Cuba
Fil: Pellón, Rolando F.. Universidad de La Habana; Cuba
Fil: Damonte, Elsa Beatriz. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description There are no specific approved drugs for the treatment of agents of viral hemorrhagic fevers (HF) and antiviral therapies against these viruses are urgently needed. The present study characterizes the potent and selective antiviral activity against the HF causing arenavirus Junin virus (JUNV) of the compound 10-allyl-6-chloro-4-methoxy-9(10H)-acridone, designated 3f. The effectiveness of 3f to inhibit JUNV multiplication was not importantly affected by the initial multiplicity of infection, with similar effective concentration 50% (EC 50) values in virus yield inhibition assays performed in Vero cells in the range of 0.2-40 plaque forming units (PFU)/cell. Mechanistic studies demonstrated that 3f did not affect the initial steps of adsorption and internalization. The subsequent process of viral RNA synthesis was strongly inhibited, as quantified by real time RT-PCR in compound-treated cells relative to non-treated cells. The addition of exogenous guanosine rescued the infectivity and RNA synthesis of JUNV in 3f-treated cells in a dose-dependent manner, but the reversal was partial, suggesting that the reduction of the GTP pool contributed to the antiviral activity of 3f, but it was not the main operative mechanism. The comparison of 3f with two other viral RNA inhibitors, ribavirin and mycophenolic acid, showed that ribavirin did not act against JUNV through the cellular enzyme inosine monophosphate dehydrogenase (IMPDH) inhibition whereas the anti-JUNV activity of mycophenolic acid was mainly targeted at this enzyme.
publishDate 2012
dc.date.none.fl_str_mv 2012-01
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/11336/114259
Sepúlveda, Claudia Soledad; García, Cybele C.; Fascio, Mirta Liliana; D'accorso, Norma Beatriz; Docampo Palacios, Maite L.; et al.; Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative; Elsevier Science; Antiviral Research; 93; 1; 1-2012; 16-22
0166-3542
CONICET Digital
CONICET
url http://hdl.handle.net/11336/114259
identifier_str_mv Sepúlveda, Claudia Soledad; García, Cybele C.; Fascio, Mirta Liliana; D'accorso, Norma Beatriz; Docampo Palacios, Maite L.; et al.; Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative; Elsevier Science; Antiviral Research; 93; 1; 1-2012; 16-22
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://www.sciencedirect.com/science/article/abs/pii/S0166354211004578
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.antiviral.2011.10.007
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
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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score 13.070432

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