Amidic derivatives of valproic acid as antiviral in HSV-1-infected oligodendrocytes.

Herpes simplex virus type 1 (HSV-1) is a ubiquitous infectious agent that can establish latency in neurons, and in some cases, viral retrograde transport results in infection of the central nervous system (CNS). Several antivirals have been identified with the ability to inhibit HSV-1 replication in...

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Autores: Praena, Beatriz, Bello-Morales, Raquel, Castro Soubriet, Fernando de, López-Guerrero, José Antonio
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/203292
Acceso en línea:http://hdl.handle.net/10261/203292
Access Level:acceso abierto
Palabra clave:HSV-1
Virus
VPD
VCD
Oligodendrocytes
Primary cells
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spelling Amidic derivatives of valproic acid as antiviral in HSV-1-infected oligodendrocytes.Praena, BeatrizBello-Morales, RaquelCastro Soubriet, Fernando deLópez-Guerrero, José AntonioHSV-1VirusVPDVCDOligodendrocytesPrimary cellsHerpes simplex virus type 1 (HSV-1) is a ubiquitous infectious agent that can establish latency in neurons, and in some cases, viral retrograde transport results in infection of the central nervous system (CNS). Several antivirals have been identified with the ability to inhibit HSV-1 replication in human cells to a greater or lesser degree, most of which are nucleoside analogues that unfortunately exhibit teratogenic potential, mbryotoxicity, carcinogenic or antiproliferative activities and resistances in immunocompromised patients, specially. In the present study, we assessed two amidic derivatives of valproic acid (VPA) – valpromide (VPD) and valnoctamide (VCD) – which are already used in clinic treatments, as feasible HSV-1 antivirals in glial cells. Both VPD and VCD have exhibited increased efficacy in bipolar disorders and as anticonvulsant drugs compared to VPA, while being less teratogenic and hepatotoxic. Cytotoxicity assays carried out in our laboratory showed that VPD and VCD were not toxic in a human oligodendroglioma cell line (HOG), at least at the concentrations established for human treatments. Infectivity assays showed a significant inhibition of HSV-1 infection in HOG cells after VPD and VCD treatment, being more pronounced in VPD-treated cells, comparable to the effects obtained with acyclovir. Furthermore, the same antiherpetic effects of VPD were observed in other oligodendrocytic cell lines and rat primary oligodendrocytes (OPCs), confirming the results obtained in HOG cells. Altogether, our results allow us to propose VPD as a potential antiherpetic drug that is able to act directly on oligodendrocytes of the CNS.We are grateful to P. Desai for the K26-GFP virus and A. T. Campagnoni for the HOG cell line. Alejandro Molina, from the Optical and Confocal Microscopy Service of CBMSO, is also acknowledged for his assistance with the confocal microscope. We are also grateful to Manuel Belda and Laura Tabera, members of the Genomics Core Facility at CBMSO, for their technical assistance. Silvia Andrade is also acknowledged for her technical assistance with flow cytometer. We thank Pablo Sosa and Mario Lozano from Cajal Institute, for OPC extraction and purification assistance. Financial support for the study was provided by the Fundación Severo Ochoa-Aeromédica Canaria and Ministerio de Ciencia, Investigación e Innovación, Spain (SAF2016-77575-R and RD16-0060-0019). The professional editing service NB Revisions was used for technical preparation of the text prior to submission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.ElsevierMinisterio de Ciencia, Innovación y Universidades (España)Fundación Severo OchoaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/203292reponame: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 2017-2020/RD16-0060-0019http://dx.doi.org/10.1016/j.antiviral.2019.05.006Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2032922026-05-22T06:33:51Z
dc.title.none.fl_str_mv Amidic derivatives of valproic acid as antiviral in HSV-1-infected oligodendrocytes.
title Amidic derivatives of valproic acid as antiviral in HSV-1-infected oligodendrocytes.
spellingShingle Amidic derivatives of valproic acid as antiviral in HSV-1-infected oligodendrocytes.
Praena, Beatriz
HSV-1
Virus
VPD
VCD
Oligodendrocytes
Primary cells
title_short Amidic derivatives of valproic acid as antiviral in HSV-1-infected oligodendrocytes.
title_full Amidic derivatives of valproic acid as antiviral in HSV-1-infected oligodendrocytes.
title_fullStr Amidic derivatives of valproic acid as antiviral in HSV-1-infected oligodendrocytes.
title_full_unstemmed Amidic derivatives of valproic acid as antiviral in HSV-1-infected oligodendrocytes.
title_sort Amidic derivatives of valproic acid as antiviral in HSV-1-infected oligodendrocytes.
dc.creator.none.fl_str_mv Praena, Beatriz
Bello-Morales, Raquel
Castro Soubriet, Fernando de
López-Guerrero, José Antonio
author Praena, Beatriz
author_facet Praena, Beatriz
Bello-Morales, Raquel
Castro Soubriet, Fernando de
López-Guerrero, José Antonio
author_role author
author2 Bello-Morales, Raquel
Castro Soubriet, Fernando de
López-Guerrero, José Antonio
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Fundación Severo Ochoa
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv HSV-1
Virus
VPD
VCD
Oligodendrocytes
Primary cells
topic HSV-1
Virus
VPD
VCD
Oligodendrocytes
Primary cells
description Herpes simplex virus type 1 (HSV-1) is a ubiquitous infectious agent that can establish latency in neurons, and in some cases, viral retrograde transport results in infection of the central nervous system (CNS). Several antivirals have been identified with the ability to inhibit HSV-1 replication in human cells to a greater or lesser degree, most of which are nucleoside analogues that unfortunately exhibit teratogenic potential, mbryotoxicity, carcinogenic or antiproliferative activities and resistances in immunocompromised patients, specially. In the present study, we assessed two amidic derivatives of valproic acid (VPA) – valpromide (VPD) and valnoctamide (VCD) – which are already used in clinic treatments, as feasible HSV-1 antivirals in glial cells. Both VPD and VCD have exhibited increased efficacy in bipolar disorders and as anticonvulsant drugs compared to VPA, while being less teratogenic and hepatotoxic. Cytotoxicity assays carried out in our laboratory showed that VPD and VCD were not toxic in a human oligodendroglioma cell line (HOG), at least at the concentrations established for human treatments. Infectivity assays showed a significant inhibition of HSV-1 infection in HOG cells after VPD and VCD treatment, being more pronounced in VPD-treated cells, comparable to the effects obtained with acyclovir. Furthermore, the same antiherpetic effects of VPD were observed in other oligodendrocytic cell lines and rat primary oligodendrocytes (OPCs), confirming the results obtained in HOG cells. Altogether, our results allow us to propose VPD as a potential antiherpetic drug that is able to act directly on oligodendrocytes of the CNS.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/203292
url http://hdl.handle.net/10261/203292
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 2017-2020/RD16-0060-0019
http://dx.doi.org/10.1016/j.antiviral.2019.05.006
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
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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