Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone

© 2024 Balsera-Manzanero, Ghirga, Ruiz-Molina, Mori, Pachón, Botta, Cordero, Quaglio and Sánchez-Céspedes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the...

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Autores: Balsera-Manzanero, María, Ghirga, Francesca, Ruiz-Molina, Ana, Mori, Mattia, Pachón, Jerónimo, Botta, Bruno, Cordero-Matía, Elisa, Quaglio, Deborah, Sánchez-Céspedes, Javier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/353601
Acceso en línea:http://hdl.handle.net/10261/353601
Access Level:acceso abierto
Palabra clave:Rotenoids
Adenovirus infection
Antiviral compound
Cytomegalovirus
Microtubular polymerization
id ES_fc9a7554ab52b7b42dba9b2fcbfe79bf
oai_identifier_str oai:digital.csic.es:10261/353601
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone
title Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone
spellingShingle Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone
Balsera-Manzanero, María
Rotenoids
Adenovirus infection
Antiviral compound
Cytomegalovirus
Microtubular polymerization
title_short Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone
title_full Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone
title_fullStr Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone
title_full_unstemmed Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone
title_sort Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone
dc.creator.none.fl_str_mv Balsera-Manzanero, María
Ghirga, Francesca
Ruiz-Molina, Ana
Mori, Mattia
Pachón, Jerónimo
Botta, Bruno
Cordero-Matía, Elisa
Quaglio, Deborah
Sánchez-Céspedes, Javier
author Balsera-Manzanero, María
author_facet Balsera-Manzanero, María
Ghirga, Francesca
Ruiz-Molina, Ana
Mori, Mattia
Pachón, Jerónimo
Botta, Bruno
Cordero-Matía, Elisa
Quaglio, Deborah
Sánchez-Céspedes, Javier
author_role author
author2 Ghirga, Francesca
Ruiz-Molina, Ana
Mori, Mattia
Pachón, Jerónimo
Botta, Bruno
Cordero-Matía, Elisa
Quaglio, Deborah
Sánchez-Céspedes, Javier
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv European Commission
Instituto de Salud Carlos III
Ministerio de Economía y Competitividad (España)
Red Española de Investigación en Patología Infecciosa
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España)
Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
Servicio Andaluz de Salud
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Rotenoids
Adenovirus infection
Antiviral compound
Cytomegalovirus
Microtubular polymerization
topic Rotenoids
Adenovirus infection
Antiviral compound
Cytomegalovirus
Microtubular polymerization
description © 2024 Balsera-Manzanero, Ghirga, Ruiz-Molina, Mori, Pachón, Botta, Cordero, Quaglio and Sánchez-Céspedes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
publishDate 2023
dc.date.none.fl_str_mv 2023
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/10261/353601
url http://hdl.handle.net/10261/353601
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/MINECO//RD16%2F0016%2F0009
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01191
info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/DTS20%2F00010
https://doi.org/10.3389/fphar.2023.1293296
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 Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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
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spelling Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenoneBalsera-Manzanero, MaríaGhirga, FrancescaRuiz-Molina, AnaMori, MattiaPachón, JerónimoBotta, BrunoCordero-Matía, ElisaQuaglio, DeborahSánchez-Céspedes, JavierRotenoidsAdenovirus infectionAntiviral compoundCytomegalovirusMicrotubular polymerization© 2024 Balsera-Manzanero, Ghirga, Ruiz-Molina, Mori, Pachón, Botta, Cordero, Quaglio and Sánchez-Céspedes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Regardless of the clinical impact of human adenovirus (HAdV) infections in the healthy population and its high morbidity in immunosuppressed patients, a specific treatment is still not yet available. In this study, we screened the CM1407 COST Action’s chemical library, comprising 1,233 natural products to identify compounds that restrict HAdV infection. Among them, we identified rotenolone, a compound that significantly inhibited HAdV infection. Next, we selected four isoflavonoid-type compounds (e.g., rotenone, deguelin, millettone, and tephrosin), namely rotenoids, structurally related to rotenolone in order to evaluate and characterized in vitro their antiviral activities against HAdV and human cytomegalovirus (HCMV). Their IC50 values for HAdV ranged from 0.0039 µM for rotenone to 0.07 µM for tephrosin, with selective indices ranging from 164.1 for rotenone to 2,429.3 for deguelin. In addition, the inhibition of HCMV replication ranged from 50% to 92.1% at twice the IC50 concentrations obtained in the plaque assay for each compound against HAdV. Our results indicated that the mechanisms of action of rotenolone, deguelin, and tephrosin involve the late stages of the HAdV replication cycle. However, the antiviral mechanism of action of rotenone appears to involve the alteration of the microtubular polymerization, which prevents HAdV particles from reaching the nuclear membrane of the cell. These isoflavonoid-type compounds exert high antiviral activity against HAdV at nanomolar concentrations, and can be considered strong hit candidates for the development of a new class of broad-spectrum antiviral drugs.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was partially supported by EU funding within the NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT). This work was partially supported by the Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by the European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 20142020, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI18/01191), and Proyectos de Desarrollo Tecnológico en Salud (DTS20/00010). JS-C and EC (CB21/13/00006) also were supported by CIBERINFEC—Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–NextGenerationEU. JS-C is a researcher belonging to the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía, Spain.Peer reviewedFrontiers MediaEuropean CommissionInstituto de Salud Carlos IIIMinisterio de Economía y Competitividad (España)Red Española de Investigación en Patología InfecciosaCentro de Investigación Biomédica en Red de Enfermedades Infecciosas (España)Ministerio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Servicio Andaluz de SaludJunta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/353601reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//RD16%2F0016%2F0009info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI18%2F01191info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/DTS20%2F00010https://doi.org/10.3389/fphar.2023.1293296Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3536012026-05-22T06:33:51Z
score 15,811543

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