Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection

Human cytomegalovirus (HCMV) poses serious health risks, particularly for immunocompromised individuals. However, the current FDA-approved anti-HCMV drugs face challenges such as drug resistance and significant side effects, underscoring the need for alternative treatment options. Essential oil comp...

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Autores: Martín-Martín, Clara, Ruiz-Rico, María, Barat, José Manuel, García-Ríos, Estéfani, Pérez-Romero, Pilar
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:dnet:digitalcsic_::d7f94f3d5d072a9b029dffa5cfab6f44
Acceso en línea:http://hdl.handle.net/10261/427530
https://api.elsevier.com/content/abstract/scopus_id/105033383107
Access Level:acceso abierto
Palabra clave:Antiviral treatment
Eugenol
Human cytomegalovirus
Thymol
Vanillin
Viral infection and dissemination
antiviral agents
Cytomegalovirus
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spelling Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infectionMartín-Martín, ClaraRuiz-Rico, MaríaBarat, José ManuelGarcía-Ríos, EstéfaniPérez-Romero, PilarAntiviral treatmentEugenolHuman cytomegalovirusThymolVanillinViral infection and disseminationantiviral agentsCytomegalovirusHuman cytomegalovirus (HCMV) poses serious health risks, particularly for immunocompromised individuals. However, the current FDA-approved anti-HCMV drugs face challenges such as drug resistance and significant side effects, underscoring the need for alternative treatment options. Essential oil components (EOCs), including eugenol, thymol and vanillin, are recognized for their therapeutic potential. This study evaluates their antiviral effects against HCMV in epithelial (ARPE-19) and fibroblast (MRC-5) cell lines. Among the EOCs, vanillin demonstrated the highest efficacy, characterized by low toxicity and a high selectivity index in both cell types. Mechanistic differences were noted between the cell lines. In ARPE-19 cells, eugenol showed virucidal activity, inhibited viral entry and suppressed early gene expression (IE-1). Conversely, in MRC-5 cells, eugenol mainly blocked viral entry and exhibited virucidal effects. Thymol was most effective in ARPE-19 cells, where it completely suppressed IE-1 expression as a result of both inhibition of viral entry and a direct disruptive effect on IE-1 expression. In addition, thymol showed an effect on viral replication. In MRC-5 cells, thymol primarily inhibited viral entry and attachment. Vanillin exhibited dual inhibitory activity in both cell lines, blocking viral attachment and entry. In MRC-5, vanillin also appears to affect intermediate processes. Notably, combining EOCs with ganciclovir resulted in synergistic effects. The eugenol/ganciclovir combination was particularly effective in ARPE-19 cells, while thymol/ganciclovir showed enhanced efficacy in MRC-5 cells. These findings suggest that EOCs have significant potential as adjunct therapies to improve antiviral outcomes and address drug-resistant HCMV strains.This study was supported by the Spanish Ministry of Science, Innovation and University, Instituto de Salud Carlos III Grant/Award Numbers: PI20CIII-00009 (MPY303/20) and PID2021-128141OB-C21 funded by MCIN/AEI/10.13039/501100011033, by 'ERDF A way of making Europe' and by the Start-up Research Grant University Notre Dame. C.M.-M. is supported by the PFIS Program (FI22CIII/0029), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades. E.G.-R. was supported by the Generalitat Valenciana plan GenT grant no. CIDEIG/2022/028.Peer reviewedMicrobiology SocietyMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Generalitat ValencianaEuropean CommissionInstituto de Salud Carlos IIIUniversity of Notre DameConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202620262026info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/427530https://api.elsevier.com/content/abstract/scopus_id/105033383107reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-128141OB-C21The Journal of general virologyThe underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1099/jgv.0.002248https://doi.org/10.1099/jgv.0.002248Síinfo:eu-repo/semantics/openAccessoai:dnet:digitalcsic_::d7f94f3d5d072a9b029dffa5cfab6f442026-05-22T06:33:51Z
dc.title.none.fl_str_mv Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection
title Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection
spellingShingle Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection
Martín-Martín, Clara
Antiviral treatment
Eugenol
Human cytomegalovirus
Thymol
Vanillin
Viral infection and dissemination
antiviral agents
Cytomegalovirus
title_short Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection
title_full Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection
title_fullStr Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection
title_full_unstemmed Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection
title_sort Decoding the antiviral potential of eugenol, thymol and vanillin against human cytomegalovirus infection
dc.creator.none.fl_str_mv Martín-Martín, Clara
Ruiz-Rico, María
Barat, José Manuel
García-Ríos, Estéfani
Pérez-Romero, Pilar
author Martín-Martín, Clara
author_facet Martín-Martín, Clara
Ruiz-Rico, María
Barat, José Manuel
García-Ríos, Estéfani
Pérez-Romero, Pilar
author_role author
author2 Ruiz-Rico, María
Barat, José Manuel
García-Ríos, Estéfani
Pérez-Romero, Pilar
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Generalitat Valenciana
European Commission
Instituto de Salud Carlos III
University of Notre Dame
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Antiviral treatment
Eugenol
Human cytomegalovirus
Thymol
Vanillin
Viral infection and dissemination
antiviral agents
Cytomegalovirus
topic Antiviral treatment
Eugenol
Human cytomegalovirus
Thymol
Vanillin
Viral infection and dissemination
antiviral agents
Cytomegalovirus
description Human cytomegalovirus (HCMV) poses serious health risks, particularly for immunocompromised individuals. However, the current FDA-approved anti-HCMV drugs face challenges such as drug resistance and significant side effects, underscoring the need for alternative treatment options. Essential oil components (EOCs), including eugenol, thymol and vanillin, are recognized for their therapeutic potential. This study evaluates their antiviral effects against HCMV in epithelial (ARPE-19) and fibroblast (MRC-5) cell lines. Among the EOCs, vanillin demonstrated the highest efficacy, characterized by low toxicity and a high selectivity index in both cell types. Mechanistic differences were noted between the cell lines. In ARPE-19 cells, eugenol showed virucidal activity, inhibited viral entry and suppressed early gene expression (IE-1). Conversely, in MRC-5 cells, eugenol mainly blocked viral entry and exhibited virucidal effects. Thymol was most effective in ARPE-19 cells, where it completely suppressed IE-1 expression as a result of both inhibition of viral entry and a direct disruptive effect on IE-1 expression. In addition, thymol showed an effect on viral replication. In MRC-5 cells, thymol primarily inhibited viral entry and attachment. Vanillin exhibited dual inhibitory activity in both cell lines, blocking viral attachment and entry. In MRC-5, vanillin also appears to affect intermediate processes. Notably, combining EOCs with ganciclovir resulted in synergistic effects. The eugenol/ganciclovir combination was particularly effective in ARPE-19 cells, while thymol/ganciclovir showed enhanced efficacy in MRC-5 cells. These findings suggest that EOCs have significant potential as adjunct therapies to improve antiviral outcomes and address drug-resistant HCMV strains.
publishDate 2026
dc.date.none.fl_str_mv 2026
2026
2026
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/10261/427530
https://api.elsevier.com/content/abstract/scopus_id/105033383107
url http://hdl.handle.net/10261/427530
https://api.elsevier.com/content/abstract/scopus_id/105033383107
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-128141OB-C21
The Journal of general virology
The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1099/jgv.0.002248
https://doi.org/10.1099/jgv.0.002248

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 Microbiology Society
publisher.none.fl_str_mv Microbiology Society
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
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