Multivalent Glycosylated Nanostructures for Ebola Virus Infection

The infection of humans by lethal pathogens such as Ebola and other related viruses has not been properly addressed so far. In this context, a relevant question arises: what can chemistry do in the search for new strategies and approaches to solve this emergent problem? Although initially a variety...

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Detalles Bibliográficos
Autores: Illescas Martínez, Beatriz María, Rojo, Javier, Delgado Vázquez, Rafael, Martín León, Nazario
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/18416
Acceso en línea:https://hdl.handle.net/20.500.14352/18416
Access Level:acceso abierto
Palabra clave:547
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spelling Multivalent Glycosylated Nanostructures for Ebola Virus InfectionIllescas Martínez, Beatriz MaríaRojo, JavierDelgado Vázquez, RafaelMartín León, Nazario547Química orgánica (Química)2306 Química OrgánicaThe infection of humans by lethal pathogens such as Ebola and other related viruses has not been properly addressed so far. In this context, a relevant question arises: what can chemistry do in the search for new strategies and approaches to solve this emergent problem? Although initially a variety of known chemical compounds – for other purposes – have been disappointingly tested against Ebola virus infection, more recently, specific molecules have been prepared. In this Perspective, we present a new approach directed to the design of efficient entry inhibitors to minimize the development of resistance by viral mutations. In particular, we focused on dendrimers as well as fullerene C60 – with a unique symmetrical and 3D globular structure – as biocompatible carbon platforms for the multivalent presentation of carbohydrates. The antiviral activity of these compounds in an Ebola pseudotyped infection model were in the low micromolar range for fullerenes with 12 and 36 mannoses. However, new tridecafullerenes – in which the central alkyne scaffold of [60]fullerene has been connected to 12 sugar-containing [60]fullerene units (total 120 mannoses)– exhibit an outstanding antiviral activity with IC50 in the subnanomolar range! The multivalent presentation of specific carbohydrates by using 3D fullerenes as controlled biocompatible carbon scaffolds represents a real advance being currently the most efficient molecules in vitro against Ebola virus infection. However, additional studies are needed to determine the optimized fullerene-based leads for practical applications.ACSUniversidad Complutense de Madrid20172017-01-0120172017-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/18416reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/184162026-06-02T12:44:21Z
dc.title.none.fl_str_mv Multivalent Glycosylated Nanostructures for Ebola Virus Infection
title Multivalent Glycosylated Nanostructures for Ebola Virus Infection
spellingShingle Multivalent Glycosylated Nanostructures for Ebola Virus Infection
Illescas Martínez, Beatriz María
547
Química orgánica (Química)
2306 Química Orgánica
title_short Multivalent Glycosylated Nanostructures for Ebola Virus Infection
title_full Multivalent Glycosylated Nanostructures for Ebola Virus Infection
title_fullStr Multivalent Glycosylated Nanostructures for Ebola Virus Infection
title_full_unstemmed Multivalent Glycosylated Nanostructures for Ebola Virus Infection
title_sort Multivalent Glycosylated Nanostructures for Ebola Virus Infection
dc.creator.none.fl_str_mv Illescas Martínez, Beatriz María
Rojo, Javier
Delgado Vázquez, Rafael
Martín León, Nazario
author Illescas Martínez, Beatriz María
author_facet Illescas Martínez, Beatriz María
Rojo, Javier
Delgado Vázquez, Rafael
Martín León, Nazario
author_role author
author2 Rojo, Javier
Delgado Vázquez, Rafael
Martín León, Nazario
author2_role author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 547
Química orgánica (Química)
2306 Química Orgánica
topic 547
Química orgánica (Química)
2306 Química Orgánica
description The infection of humans by lethal pathogens such as Ebola and other related viruses has not been properly addressed so far. In this context, a relevant question arises: what can chemistry do in the search for new strategies and approaches to solve this emergent problem? Although initially a variety of known chemical compounds – for other purposes – have been disappointingly tested against Ebola virus infection, more recently, specific molecules have been prepared. In this Perspective, we present a new approach directed to the design of efficient entry inhibitors to minimize the development of resistance by viral mutations. In particular, we focused on dendrimers as well as fullerene C60 – with a unique symmetrical and 3D globular structure – as biocompatible carbon platforms for the multivalent presentation of carbohydrates. The antiviral activity of these compounds in an Ebola pseudotyped infection model were in the low micromolar range for fullerenes with 12 and 36 mannoses. However, new tridecafullerenes – in which the central alkyne scaffold of [60]fullerene has been connected to 12 sugar-containing [60]fullerene units (total 120 mannoses)– exhibit an outstanding antiviral activity with IC50 in the subnanomolar range! The multivalent presentation of specific carbohydrates by using 3D fullerenes as controlled biocompatible carbon scaffolds represents a real advance being currently the most efficient molecules in vitro against Ebola virus infection. However, additional studies are needed to determine the optimized fullerene-based leads for practical applications.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01
2017
2017-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/18416
url https://hdl.handle.net/20.500.14352/18416
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv ACS
publisher.none.fl_str_mv ACS
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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