In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses

Autores
Gonzalez, Maria Micaela; Vizoso Pinto, María Guadalupe; Erra Balsells, Rosa; Gensch, Thomas; Cabrerizo, Franco Martín
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Herpes simplex virus (HSV) infections are highly widespread among humans, producingsymptoms ranging from ulcerative lesions to severe diseases such as blindness and life-threateningencephalitis. At present, there are no vaccines available, and some existing antiviral treatments canbe ineffective or lead to adverse effects. As a result, there is a need for new anti-HSV drugs. In thisreport, the in vitro anti-HSV effect of 9,9′-norharmane dimer (nHo-dimer), which belongs to the β-carboline (βC) alkaloid family, was evaluated. The dimer exhibited no virucidal properties and didnot impede either the aachment or penetration steps of viral particles. The antiviral effect was onlyexerted under the constant presence of the dimer in the incubation media, and the mechanism ofaction was found to involve later events of virus infection. Analysis of fluorescence lifetime imagingdata showed that the nHo-dimer internalized well into the cells when present in the extracellularincubation medium, with a preferential accumulation into perinuclear organelles including mitochondria.After washing the host cells with fresh medium free of nHo-dimer, the signal decreased,suggesting the partial release of the compound from the cells. This agrees with the observation thatthe antiviral effect is solely manifested when the alkaloid is consistently present in the incubationmedia.
Fil: Gonzalez, Maria Micaela. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Erra Balsells, Rosa. 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: Gensch, Thomas. Helmholtz Gemeinschaft. Forschungszentrum Jülich; Alemania
Fil: Cabrerizo, Franco Martín. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Materia
β-carbolines
alkaloids
herpes simplex-1
herpes simplex-2
cellular uptake
cytotoxicity
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/237809
Acceder
id CONICETDig_01941e155e478b6431a32823444a58ed
oai_identifier_str oai:ri.conicet.gov.ar:11336/237809
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex VirusesGonzalez, Maria MicaelaVizoso Pinto, María GuadalupeErra Balsells, RosaGensch, ThomasCabrerizo, Franco Martínβ-carbolinesalkaloidsherpes simplex-1herpes simplex-2cellular uptakecytotoxicityhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Herpes simplex virus (HSV) infections are highly widespread among humans, producingsymptoms ranging from ulcerative lesions to severe diseases such as blindness and life-threateningencephalitis. At present, there are no vaccines available, and some existing antiviral treatments canbe ineffective or lead to adverse effects. As a result, there is a need for new anti-HSV drugs. In thisreport, the in vitro anti-HSV effect of 9,9′-norharmane dimer (nHo-dimer), which belongs to the β-carboline (βC) alkaloid family, was evaluated. The dimer exhibited no virucidal properties and didnot impede either the aachment or penetration steps of viral particles. The antiviral effect was onlyexerted under the constant presence of the dimer in the incubation media, and the mechanism ofaction was found to involve later events of virus infection. Analysis of fluorescence lifetime imagingdata showed that the nHo-dimer internalized well into the cells when present in the extracellularincubation medium, with a preferential accumulation into perinuclear organelles including mitochondria.After washing the host cells with fresh medium free of nHo-dimer, the signal decreased,suggesting the partial release of the compound from the cells. This agrees with the observation thatthe antiviral effect is solely manifested when the alkaloid is consistently present in the incubationmedia.Fil: Gonzalez, Maria Micaela. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaFil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Erra Balsells, Rosa. 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: Gensch, Thomas. Helmholtz Gemeinschaft. Forschungszentrum Jülich; AlemaniaFil: Cabrerizo, Franco Martín. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; ArgentinaMolecular Diversity Preservation International2024-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/237809Gonzalez, Maria Micaela; Vizoso Pinto, María Guadalupe; Erra Balsells, Rosa; Gensch, Thomas; Cabrerizo, Franco Martín; In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 25; 9; 5-2024; 1-191422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/25/9/4966info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms25094966info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:05Zoai:ri.conicet.gov.ar:11336/237809instacron: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 09:45:05.966CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses
title In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses
spellingShingle In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses
Gonzalez, Maria Micaela
β-carbolines
alkaloids
herpes simplex-1
herpes simplex-2
cellular uptake
cytotoxicity
title_short In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses
title_full In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses
title_fullStr In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses
title_full_unstemmed In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses
title_sort In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses
dc.creator.none.fl_str_mv Gonzalez, Maria Micaela
Vizoso Pinto, María Guadalupe
Erra Balsells, Rosa
Gensch, Thomas
Cabrerizo, Franco Martín
author Gonzalez, Maria Micaela
author_facet Gonzalez, Maria Micaela
Vizoso Pinto, María Guadalupe
Erra Balsells, Rosa
Gensch, Thomas
Cabrerizo, Franco Martín
author_role author
author2 Vizoso Pinto, María Guadalupe
Erra Balsells, Rosa
Gensch, Thomas
Cabrerizo, Franco Martín
author2_role author
author
author
author
dc.subject.none.fl_str_mv β-carbolines
alkaloids
herpes simplex-1
herpes simplex-2
cellular uptake
cytotoxicity
topic β-carbolines
alkaloids
herpes simplex-1
herpes simplex-2
cellular uptake
cytotoxicity
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Herpes simplex virus (HSV) infections are highly widespread among humans, producingsymptoms ranging from ulcerative lesions to severe diseases such as blindness and life-threateningencephalitis. At present, there are no vaccines available, and some existing antiviral treatments canbe ineffective or lead to adverse effects. As a result, there is a need for new anti-HSV drugs. In thisreport, the in vitro anti-HSV effect of 9,9′-norharmane dimer (nHo-dimer), which belongs to the β-carboline (βC) alkaloid family, was evaluated. The dimer exhibited no virucidal properties and didnot impede either the aachment or penetration steps of viral particles. The antiviral effect was onlyexerted under the constant presence of the dimer in the incubation media, and the mechanism ofaction was found to involve later events of virus infection. Analysis of fluorescence lifetime imagingdata showed that the nHo-dimer internalized well into the cells when present in the extracellularincubation medium, with a preferential accumulation into perinuclear organelles including mitochondria.After washing the host cells with fresh medium free of nHo-dimer, the signal decreased,suggesting the partial release of the compound from the cells. This agrees with the observation thatthe antiviral effect is solely manifested when the alkaloid is consistently present in the incubationmedia.
Fil: Gonzalez, Maria Micaela. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
Fil: Vizoso Pinto, María Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Erra Balsells, Rosa. 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: Gensch, Thomas. Helmholtz Gemeinschaft. Forschungszentrum Jülich; Alemania
Fil: Cabrerizo, Franco Martín. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
description Herpes simplex virus (HSV) infections are highly widespread among humans, producingsymptoms ranging from ulcerative lesions to severe diseases such as blindness and life-threateningencephalitis. At present, there are no vaccines available, and some existing antiviral treatments canbe ineffective or lead to adverse effects. As a result, there is a need for new anti-HSV drugs. In thisreport, the in vitro anti-HSV effect of 9,9′-norharmane dimer (nHo-dimer), which belongs to the β-carboline (βC) alkaloid family, was evaluated. The dimer exhibited no virucidal properties and didnot impede either the aachment or penetration steps of viral particles. The antiviral effect was onlyexerted under the constant presence of the dimer in the incubation media, and the mechanism ofaction was found to involve later events of virus infection. Analysis of fluorescence lifetime imagingdata showed that the nHo-dimer internalized well into the cells when present in the extracellularincubation medium, with a preferential accumulation into perinuclear organelles including mitochondria.After washing the host cells with fresh medium free of nHo-dimer, the signal decreased,suggesting the partial release of the compound from the cells. This agrees with the observation thatthe antiviral effect is solely manifested when the alkaloid is consistently present in the incubationmedia.
publishDate 2024
dc.date.none.fl_str_mv 2024-05
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/11336/237809
Gonzalez, Maria Micaela; Vizoso Pinto, María Guadalupe; Erra Balsells, Rosa; Gensch, Thomas; Cabrerizo, Franco Martín; In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 25; 9; 5-2024; 1-19
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/237809
identifier_str_mv Gonzalez, Maria Micaela; Vizoso Pinto, María Guadalupe; Erra Balsells, Rosa; Gensch, Thomas; Cabrerizo, Franco Martín; In Vitro Effect of 9,9′-Norharmane Dimer against Herpes Simplex Viruses; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 25; 9; 5-2024; 1-19
1422-0067
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.mdpi.com/1422-0067/25/9/4966
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms25094966
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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 13.13397

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