Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides

Novel strategies in the design of HIV-1 fusion/entry inhibitors are based on the construction of dual-targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual-targeting peptides composed of peptide domains of E2 and E1 envelope proteins f...

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Autores: Gómara Elena, María José, Pérez, Yolanda, Martínez, Javier P., Barnadas-Rodríguez, Ramon, Schultz, Anke, Briesen, Hagen von, Perálvarez-Marín, Alex, Meyerhans, Andreas, Haro Villar, Isabel
Tipo de recurso: artículo
Estado:Versión publicada
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:10261/177915
Acceso en línea:http://hdl.handle.net/10261/177915
Access Level:acceso abierto
Palabra clave:Peptides
Human pegivirus
HIV-1
Antivirals
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spelling Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptidesGómara Elena, María JoséPérez, YolandaMartínez, Javier P.Barnadas-Rodríguez, RamonSchultz, AnkeBriesen, Hagen vonPerálvarez-Marín, AlexMeyerhans, AndreasHaro Villar, IsabelPeptidesHuman pegivirusHIV-1AntiviralsNovel strategies in the design of HIV-1 fusion/entry inhibitors are based on the construction of dual-targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual-targeting peptides composed of peptide domains of E2 and E1 envelope proteins from Human Pegivirus with the aim of targeting both the loop region and the fusion peptide domains of HIV-1 gp41. In a previous work, we described the inhibitory role of a highly conserved fragment of the E1 protein (domain 139–156) which interacts with the HIV-1 fusion peptide at the membrane level. Here, two different dual-targeting peptides, where this E1 peptide is located on the N- or the C-terminus respectively, have been chemically synthesized and their antiviral activities have been evaluated with HIV pseudotyped viruses from different clades. The study of the functional behaviour of peptides in a membranous environment attending to the peptide recognition of the target sites on gp41, the peptide conformation as well as the peptide affinity to the membrane, demonstrate that antiviral activity of the dual-targeting peptides is directly related to the peptide affinity and its subsequent assembly into the model membrane. The overall results point out to the necessity that fusion inhibitor peptides that specifically interfere with the N-terminal region of gp41 are embedded within the membrane in order to properly interact with their viral target. © 2019, The Author(s).Financial support from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and the European Regional Development Fund (Grant CTQ2015-63919-R) is gratefully acknowledged. JM and AM were supported by a grant from the Spanish Ministry of Economy, Industry and Competitive-ness and FEDER grant SAF2016-75505-R (AEI/MINECO/FEDER, UE) and through the “María de Maeztu” Programme for Units of Excellence in R&D (MDM-2014-0370). Partial financial support from the Spanish National Research Council (CSIC) is also gratefully acknowledged.Peer reviewedSpringer NatureMinisterio de Economía y Competitividad (España)European CommissionMinisterio de Economía, Industria y Competitividad (España)Consejo Superior de Investigaciones Científicas (España)Gómara, María José [0000-0002-6906-4833]Haro, Isabel [0000-0001-8677-2340]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]201920192019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/177915reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2015-63919-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-75505-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/MDM-2014-0370https://doi.org/10.1038/s41598-019-40125-4Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1779152026-05-22T06:33:51Z
dc.title.none.fl_str_mv Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides
title Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides
spellingShingle Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides
Gómara Elena, María José
Peptides
Human pegivirus
HIV-1
Antivirals
title_short Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides
title_full Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides
title_fullStr Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides
title_full_unstemmed Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides
title_sort Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides
dc.creator.none.fl_str_mv Gómara Elena, María José
Pérez, Yolanda
Martínez, Javier P.
Barnadas-Rodríguez, Ramon
Schultz, Anke
Briesen, Hagen von
Perálvarez-Marín, Alex
Meyerhans, Andreas
Haro Villar, Isabel
author Gómara Elena, María José
author_facet Gómara Elena, María José
Pérez, Yolanda
Martínez, Javier P.
Barnadas-Rodríguez, Ramon
Schultz, Anke
Briesen, Hagen von
Perálvarez-Marín, Alex
Meyerhans, Andreas
Haro Villar, Isabel
author_role author
author2 Pérez, Yolanda
Martínez, Javier P.
Barnadas-Rodríguez, Ramon
Schultz, Anke
Briesen, Hagen von
Perálvarez-Marín, Alex
Meyerhans, Andreas
Haro Villar, Isabel
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Ministerio de Economía, Industria y Competitividad (España)
Consejo Superior de Investigaciones Científicas (España)
Gómara, María José [0000-0002-6906-4833]
Haro, Isabel [0000-0001-8677-2340]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Peptides
Human pegivirus
HIV-1
Antivirals
topic Peptides
Human pegivirus
HIV-1
Antivirals
description Novel strategies in the design of HIV-1 fusion/entry inhibitors are based on the construction of dual-targeting fusion proteins and peptides with synergistic antiviral effects. In this work we describe the design of dual-targeting peptides composed of peptide domains of E2 and E1 envelope proteins from Human Pegivirus with the aim of targeting both the loop region and the fusion peptide domains of HIV-1 gp41. In a previous work, we described the inhibitory role of a highly conserved fragment of the E1 protein (domain 139–156) which interacts with the HIV-1 fusion peptide at the membrane level. Here, two different dual-targeting peptides, where this E1 peptide is located on the N- or the C-terminus respectively, have been chemically synthesized and their antiviral activities have been evaluated with HIV pseudotyped viruses from different clades. The study of the functional behaviour of peptides in a membranous environment attending to the peptide recognition of the target sites on gp41, the peptide conformation as well as the peptide affinity to the membrane, demonstrate that antiviral activity of the dual-targeting peptides is directly related to the peptide affinity and its subsequent assembly into the model membrane. The overall results point out to the necessity that fusion inhibitor peptides that specifically interfere with the N-terminal region of gp41 are embedded within the membrane in order to properly interact with their viral target. © 2019, The Author(s).
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
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/10261/177915
url http://hdl.handle.net/10261/177915
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2015-63919-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-75505-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/MDM-2014-0370
https://doi.org/10.1038/s41598-019-40125-4
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
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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