Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture

Autores
Hollmann, Axel; Gonçalves, Sónia; Augusto, Marcelo T.; Castanho, Miguel A.R.B.; Lee, Benhur; Santos, Nuno C.
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Targeting membranes of enveloped viruses represents an exciting new paradigm to explore on the development of broad-spectrum antivirals. Recently, broad-spectrum small-molecule antiviral drugs were described, preventing enveloped virus entry at an intermediate step, after virus binding but before virus-cell fusion. Those compounds, including an oxazolidine-2,4-dithione named JL103 that presented the most promissing results, act deleteriously on the virus envelope but not at the cell membrane level. In this work, by using atomic force microscopy (AFM), we aimed at unraveling the effects that JL103 is able to induce in the lipid membrane architecture at the nanoscale. Our results indicate that singlet oxygen produced by JL103 decreases membrane thickness, with an expansion of the area per phospholipid, by attacking the double bonds of unsaturated phospholipids. This membrane reorganization prevents the fusion between enveloped virus and target cell membranes, resulting in viral entry inhibition. From the Clinical Editor: The recent development of a family of innovative broad-spectrum small-molecule antiviral drugs that block virus cell entry has provided exciting armors against viruses. In this research paper, the authors utilize atomic force microscopy to investigate the mechanism of action of viral blockade. The findings have resulted in new understanding of cell membrane behavior, which may help in further drug design.
Fil: Hollmann, Axel. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gonçalves, Sónia. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal
Fil: Augusto, Marcelo T.. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal
Fil: Castanho, Miguel A.R.B.. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal
Fil: Lee, Benhur. Icahn School of Medicine at Mount Sinai. Department of Microbiology; Estados Unidos
Fil: Santos, Nuno C.. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal
Materia
AFM
BROAD-SPECTRUM ANTIVIRAL
MEMBRANE ORGANIZATION
SINGLET OXYGEN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/38383
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/38383
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitectureHollmann, AxelGonçalves, SóniaAugusto, Marcelo T.Castanho, Miguel A.R.B.Lee, BenhurSantos, Nuno C.AFMBROAD-SPECTRUM ANTIVIRALMEMBRANE ORGANIZATIONSINGLET OXYGENhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Targeting membranes of enveloped viruses represents an exciting new paradigm to explore on the development of broad-spectrum antivirals. Recently, broad-spectrum small-molecule antiviral drugs were described, preventing enveloped virus entry at an intermediate step, after virus binding but before virus-cell fusion. Those compounds, including an oxazolidine-2,4-dithione named JL103 that presented the most promissing results, act deleteriously on the virus envelope but not at the cell membrane level. In this work, by using atomic force microscopy (AFM), we aimed at unraveling the effects that JL103 is able to induce in the lipid membrane architecture at the nanoscale. Our results indicate that singlet oxygen produced by JL103 decreases membrane thickness, with an expansion of the area per phospholipid, by attacking the double bonds of unsaturated phospholipids. This membrane reorganization prevents the fusion between enveloped virus and target cell membranes, resulting in viral entry inhibition. From the Clinical Editor: The recent development of a family of innovative broad-spectrum small-molecule antiviral drugs that block virus cell entry has provided exciting armors against viruses. In this research paper, the authors utilize atomic force microscopy to investigate the mechanism of action of viral blockade. The findings have resulted in new understanding of cell membrane behavior, which may help in further drug design.Fil: Hollmann, Axel. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gonçalves, Sónia. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; PortugalFil: Augusto, Marcelo T.. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; PortugalFil: Castanho, Miguel A.R.B.. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; PortugalFil: Lee, Benhur. Icahn School of Medicine at Mount Sinai. Department of Microbiology; Estados UnidosFil: Santos, Nuno C.. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; PortugalElsevier Science2015-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38383Hollmann, Axel; Gonçalves, Sónia; Augusto, Marcelo T.; Castanho, Miguel A.R.B.; Lee, Benhur; et al.; Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture; Elsevier Science; Nanomedicine-nanotechnology Biology And Medicine; 11; 5; 7-2015; 1163-11671549-9634CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1549963415000647info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476930/info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nano.2015.02.014info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:31:47Zoai:ri.conicet.gov.ar:11336/38383instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:31:47.4CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture
title Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture
spellingShingle Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture
Hollmann, Axel
AFM
BROAD-SPECTRUM ANTIVIRAL
MEMBRANE ORGANIZATION
SINGLET OXYGEN
title_short Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture
title_full Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture
title_fullStr Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture
title_full_unstemmed Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture
title_sort Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture
dc.creator.none.fl_str_mv Hollmann, Axel
Gonçalves, Sónia
Augusto, Marcelo T.
Castanho, Miguel A.R.B.
Lee, Benhur
Santos, Nuno C.
author Hollmann, Axel
author_facet Hollmann, Axel
Gonçalves, Sónia
Augusto, Marcelo T.
Castanho, Miguel A.R.B.
Lee, Benhur
Santos, Nuno C.
author_role author
author2 Gonçalves, Sónia
Augusto, Marcelo T.
Castanho, Miguel A.R.B.
Lee, Benhur
Santos, Nuno C.
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv AFM
BROAD-SPECTRUM ANTIVIRAL
MEMBRANE ORGANIZATION
SINGLET OXYGEN
topic AFM
BROAD-SPECTRUM ANTIVIRAL
MEMBRANE ORGANIZATION
SINGLET OXYGEN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Targeting membranes of enveloped viruses represents an exciting new paradigm to explore on the development of broad-spectrum antivirals. Recently, broad-spectrum small-molecule antiviral drugs were described, preventing enveloped virus entry at an intermediate step, after virus binding but before virus-cell fusion. Those compounds, including an oxazolidine-2,4-dithione named JL103 that presented the most promissing results, act deleteriously on the virus envelope but not at the cell membrane level. In this work, by using atomic force microscopy (AFM), we aimed at unraveling the effects that JL103 is able to induce in the lipid membrane architecture at the nanoscale. Our results indicate that singlet oxygen produced by JL103 decreases membrane thickness, with an expansion of the area per phospholipid, by attacking the double bonds of unsaturated phospholipids. This membrane reorganization prevents the fusion between enveloped virus and target cell membranes, resulting in viral entry inhibition. From the Clinical Editor: The recent development of a family of innovative broad-spectrum small-molecule antiviral drugs that block virus cell entry has provided exciting armors against viruses. In this research paper, the authors utilize atomic force microscopy to investigate the mechanism of action of viral blockade. The findings have resulted in new understanding of cell membrane behavior, which may help in further drug design.
Fil: Hollmann, Axel. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gonçalves, Sónia. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal
Fil: Augusto, Marcelo T.. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal
Fil: Castanho, Miguel A.R.B.. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal
Fil: Lee, Benhur. Icahn School of Medicine at Mount Sinai. Department of Microbiology; Estados Unidos
Fil: Santos, Nuno C.. Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular; Portugal
description Targeting membranes of enveloped viruses represents an exciting new paradigm to explore on the development of broad-spectrum antivirals. Recently, broad-spectrum small-molecule antiviral drugs were described, preventing enveloped virus entry at an intermediate step, after virus binding but before virus-cell fusion. Those compounds, including an oxazolidine-2,4-dithione named JL103 that presented the most promissing results, act deleteriously on the virus envelope but not at the cell membrane level. In this work, by using atomic force microscopy (AFM), we aimed at unraveling the effects that JL103 is able to induce in the lipid membrane architecture at the nanoscale. Our results indicate that singlet oxygen produced by JL103 decreases membrane thickness, with an expansion of the area per phospholipid, by attacking the double bonds of unsaturated phospholipids. This membrane reorganization prevents the fusion between enveloped virus and target cell membranes, resulting in viral entry inhibition. From the Clinical Editor: The recent development of a family of innovative broad-spectrum small-molecule antiviral drugs that block virus cell entry has provided exciting armors against viruses. In this research paper, the authors utilize atomic force microscopy to investigate the mechanism of action of viral blockade. The findings have resulted in new understanding of cell membrane behavior, which may help in further drug design.
publishDate 2015
dc.date.none.fl_str_mv 2015-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/38383
Hollmann, Axel; Gonçalves, Sónia; Augusto, Marcelo T.; Castanho, Miguel A.R.B.; Lee, Benhur; et al.; Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture; Elsevier Science; Nanomedicine-nanotechnology Biology And Medicine; 11; 5; 7-2015; 1163-1167
1549-9634
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38383
identifier_str_mv Hollmann, Axel; Gonçalves, Sónia; Augusto, Marcelo T.; Castanho, Miguel A.R.B.; Lee, Benhur; et al.; Effects of singlet oxygen generated by a broad-spectrum viral fusion inhibitor on membrane nanoarchitecture; Elsevier Science; Nanomedicine-nanotechnology Biology And Medicine; 11; 5; 7-2015; 1163-1167
1549-9634
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1549963415000647
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4476930/
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nano.2015.02.014
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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