Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo

The emergent human coronavirus SARS-CoV-2 and its resistance to current drugs makes the need for new potent treatments for COVID-19 patients strongly necessary. Dextran sulfate (DS) polysaccharides have long demonstrated antiviral activity against different enveloped viruses in vitro. However, their...

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Autores: Andreu, Sabina, Von Kobbe, Cayetano, Delgado Cañaveras, María del Pilar, Ripa Peralta, Inés, Buzón, Maria J., Genescà, Meritxell, Gironés Pujol, Nuria, Moral Salmoral, Javier de, Ramírez, Gustavo A., Zúñiga Lucas, Sonia, Enjuanes Sánchez, Luis, López Guerrero, José Antonio, Bello-Morales Arroyo, Ángeles Raquel
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:10261/346859
Acceso en línea:http://hdl.handle.net/10261/346859
Access Level:acceso abierto
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spelling Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivoAndreu, SabinaVon Kobbe, CayetanoDelgado Cañaveras, María del PilarRipa Peralta, InésBuzón, Maria J.Genescà, MeritxellGironés Pujol, NuriaMoral Salmoral, Javier deRamírez, Gustavo A.Zúñiga Lucas, SoniaEnjuanes Sánchez, LuisLópez Guerrero, José AntonioBello-Morales Arroyo, Ángeles RaquelThe emergent human coronavirus SARS-CoV-2 and its resistance to current drugs makes the need for new potent treatments for COVID-19 patients strongly necessary. Dextran sulfate (DS) polysaccharides have long demonstrated antiviral activity against different enveloped viruses in vitro. However, their poor bioavailability has led to their abandonment as antiviral candidates. Here, we report for the first time the broad-spectrum antiviral activity of a DS-based extrapolymeric substance produced by the lactic acid bacterium Leuconostoc mesenteroides B512F. Time of addition assays with SARS-CoV-2 pseudoviruses in in vitro models confirm the inhibitory activity of DSs in the early stages of viral infection (viral entry). In addition, this exopolysaccharide substance also reports broad-spectrum antiviral activity against several enveloped viruses such as SARS-CoV-2, HCoV229E, HSV-1, in in vitro models and in human lung tissue. The toxicity and antiviral capacity of DS from L. mesenteroides was tested in vivo in mouse models which are susceptible to SARS-CoV-2 infection. The described DS, administered by inhalation, a new route of administration for these types of polymers, shows strong inhibition of SARS-CoV-2 infection in vivo, significantly reducing animal mortality and morbidity at non-toxic doses. Therefore, we suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.Financial support for the study was provided by the REACT-EU 2021 grant from Comunidad de Madrid to the Project COVTRAVI19-CM, Plataformas y modelos preclínicos para el abordaje multidisciplinar en COVID-19 y en respuesta a futuras pandemias.Peer reviewedFrontiers MediaComunidad de MadridEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420232024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/346859reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3389/fmicb.2023.1185504Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3468592026-05-22T06:33:51Z
dc.title.none.fl_str_mv Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo
title Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo
spellingShingle Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo
Andreu, Sabina
title_short Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo
title_full Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo
title_fullStr Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo
title_full_unstemmed Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo
title_sort Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo
dc.creator.none.fl_str_mv Andreu, Sabina
Von Kobbe, Cayetano
Delgado Cañaveras, María del Pilar
Ripa Peralta, Inés
Buzón, Maria J.
Genescà, Meritxell
Gironés Pujol, Nuria
Moral Salmoral, Javier de
Ramírez, Gustavo A.
Zúñiga Lucas, Sonia
Enjuanes Sánchez, Luis
López Guerrero, José Antonio
Bello-Morales Arroyo, Ángeles Raquel
author Andreu, Sabina
author_facet Andreu, Sabina
Von Kobbe, Cayetano
Delgado Cañaveras, María del Pilar
Ripa Peralta, Inés
Buzón, Maria J.
Genescà, Meritxell
Gironés Pujol, Nuria
Moral Salmoral, Javier de
Ramírez, Gustavo A.
Zúñiga Lucas, Sonia
Enjuanes Sánchez, Luis
López Guerrero, José Antonio
Bello-Morales Arroyo, Ángeles Raquel
author_role author
author2 Von Kobbe, Cayetano
Delgado Cañaveras, María del Pilar
Ripa Peralta, Inés
Buzón, Maria J.
Genescà, Meritxell
Gironés Pujol, Nuria
Moral Salmoral, Javier de
Ramírez, Gustavo A.
Zúñiga Lucas, Sonia
Enjuanes Sánchez, Luis
López Guerrero, José Antonio
Bello-Morales Arroyo, Ángeles Raquel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Comunidad de Madrid
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
description The emergent human coronavirus SARS-CoV-2 and its resistance to current drugs makes the need for new potent treatments for COVID-19 patients strongly necessary. Dextran sulfate (DS) polysaccharides have long demonstrated antiviral activity against different enveloped viruses in vitro. However, their poor bioavailability has led to their abandonment as antiviral candidates. Here, we report for the first time the broad-spectrum antiviral activity of a DS-based extrapolymeric substance produced by the lactic acid bacterium Leuconostoc mesenteroides B512F. Time of addition assays with SARS-CoV-2 pseudoviruses in in vitro models confirm the inhibitory activity of DSs in the early stages of viral infection (viral entry). In addition, this exopolysaccharide substance also reports broad-spectrum antiviral activity against several enveloped viruses such as SARS-CoV-2, HCoV229E, HSV-1, in in vitro models and in human lung tissue. The toxicity and antiviral capacity of DS from L. mesenteroides was tested in vivo in mouse models which are susceptible to SARS-CoV-2 infection. The described DS, administered by inhalation, a new route of administration for these types of polymers, shows strong inhibition of SARS-CoV-2 infection in vivo, significantly reducing animal mortality and morbidity at non-toxic doses. Therefore, we suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.
publishDate 2023
dc.date.none.fl_str_mv 2023
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/10261/346859
url http://hdl.handle.net/10261/346859
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3389/fmicb.2023.1185504
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
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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