Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents

Despite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus has yet to be developed. In this study, we repo...

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Autores: Balsera-Manzanero, María, Soengas, Raquel G., Carretero-Ledesma, Marta, Ratia, Carlos, Iglesias, M. José, Pachón, Jerónimo, López-Ortiz, Fernando, Cordero, Elisa, Soto, Sara M., Sánchez-Céspedes, Javier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/368307
Acceso en línea:http://hdl.handle.net/10261/368307
https://api.elsevier.com/content/abstract/scopus_id/85188257360
Access Level:acceso abierto
Palabra clave:Metallodrugs
Adenovirus
Antivirals
Cycloaurated complexes
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repository_id_str
spelling Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agentsBalsera-Manzanero, MaríaSoengas, Raquel G.Carretero-Ledesma, MartaRatia, CarlosIglesias, M. JoséPachón, JerónimoLópez-Ortiz, FernandoCordero, ElisaSoto, Sara M.Sánchez-Céspedes, JavierMetallodrugsAdenovirusAntiviralsCycloaurated complexesDespite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus has yet to be developed. In this study, we report the anti-HAdV activity of sub-micromolar concentrations of four heteroleptic (C^S)-cycloaurated complexes bearing a single thiophosphinamide [Au(dpta)Cl2, Au(dpta)(mrdtc), and Au(dpta)(dedtc)] or thiophosphonamide [Au(bpta)(dedtc)] chelating ligand and a dithiocarbamate moiety. In addition to their low cytotoxicity, the findings of mechanistic assays revealed that these molecules have antiviral activity by targeting stages of the viral replication cycle subsequent to DNA replication. Additionally, all four compounds showed a significant inhibition of human cytomegalovirus (HCMV) DNA replication, thereby providing evidence for potential broad-spectrum antiviral activity.This work was partially supported by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, co-funded by the European Development Regional Fund Proyectos de Investigación en Salud (PI18/01191, PI19/00478), and Proyectos de Desarrollo Tecnológico en Salud (DTS20/00010, DTS21/00004). JSC (CB21/13/00006) and S.M.S. (CB21/13/00081) also received support from the CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, co-funded by the European Development Regional Fund. J.S.C is supported by the program “Nicolás Monardes” (C-0059-2018) Servicio Andaluz de Salud, Junta de Andalucía. ISGlobal is a CERCA center from the Generalitat of Catalunya and a Severo Ochoa Center (Spanish Ministry of Science, Innovations, and Universities).Peer reviewedElsevierInstituto de Salud Carlos IIIMinisterio de Ciencia e Innovación (España)European CommissionCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (España)Servicio Andaluz de SaludJunta de AndalucíaGeneralitat de CatalunyaMinisterio de Ciencia, Innovación y Universidades (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/368307https://api.elsevier.com/content/abstract/scopus_id/85188257360reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésBalsera-Manzanero, María; Soengas, Raquel G.; Carretero-Ledesma, Marta; Ratia, Carlos; Iglesias, M. José; Pachón, Jerónimo; López-Ortiz, Fernando; Cordero, Elisa; Soto, Sara M.; Sánchez-Céspedes, Javier; 2024; Supporting Information Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents [Dataset]; Elsevier; https://doi.org/10.1016/j.heliyon.2024.e27601https://doi.org/10.1016/j.heliyon.2024.e27601Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3683072026-05-22T06:33:51Z
dc.title.none.fl_str_mv Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents
title Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents
spellingShingle Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents
Balsera-Manzanero, María
Metallodrugs
Adenovirus
Antivirals
Cycloaurated complexes
title_short Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents
title_full Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents
title_fullStr Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents
title_full_unstemmed Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents
title_sort Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents
dc.creator.none.fl_str_mv Balsera-Manzanero, María
Soengas, Raquel G.
Carretero-Ledesma, Marta
Ratia, Carlos
Iglesias, M. José
Pachón, Jerónimo
López-Ortiz, Fernando
Cordero, Elisa
Soto, Sara M.
Sánchez-Céspedes, Javier
author Balsera-Manzanero, María
author_facet Balsera-Manzanero, María
Soengas, Raquel G.
Carretero-Ledesma, Marta
Ratia, Carlos
Iglesias, M. José
Pachón, Jerónimo
López-Ortiz, Fernando
Cordero, Elisa
Soto, Sara M.
Sánchez-Céspedes, Javier
author_role author
author2 Soengas, Raquel G.
Carretero-Ledesma, Marta
Ratia, Carlos
Iglesias, M. José
Pachón, Jerónimo
López-Ortiz, Fernando
Cordero, Elisa
Soto, Sara M.
Sánchez-Céspedes, Javier
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Ciencia e Innovación (España)
European Commission
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España)
Servicio Andaluz de Salud
Junta de Andalucía
Generalitat de Catalunya
Ministerio de Ciencia, Innovación y Universidades (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Metallodrugs
Adenovirus
Antivirals
Cycloaurated complexes
topic Metallodrugs
Adenovirus
Antivirals
Cycloaurated complexes
description Despite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus has yet to be developed. In this study, we report the anti-HAdV activity of sub-micromolar concentrations of four heteroleptic (C^S)-cycloaurated complexes bearing a single thiophosphinamide [Au(dpta)Cl2, Au(dpta)(mrdtc), and Au(dpta)(dedtc)] or thiophosphonamide [Au(bpta)(dedtc)] chelating ligand and a dithiocarbamate moiety. In addition to their low cytotoxicity, the findings of mechanistic assays revealed that these molecules have antiviral activity by targeting stages of the viral replication cycle subsequent to DNA replication. Additionally, all four compounds showed a significant inhibition of human cytomegalovirus (HCMV) DNA replication, thereby providing evidence for potential broad-spectrum antiviral activity.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/368307
https://api.elsevier.com/content/abstract/scopus_id/85188257360
url http://hdl.handle.net/10261/368307
https://api.elsevier.com/content/abstract/scopus_id/85188257360
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Balsera-Manzanero, María; Soengas, Raquel G.; Carretero-Ledesma, Marta; Ratia, Carlos; Iglesias, M. José; Pachón, Jerónimo; López-Ortiz, Fernando; Cordero, Elisa; Soto, Sara M.; Sánchez-Céspedes, Javier; 2024; Supporting Information Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents [Dataset]; Elsevier; https://doi.org/10.1016/j.heliyon.2024.e27601
https://doi.org/10.1016/j.heliyon.2024.e27601
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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