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

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  • dc.contributor.author Gomara, Maria J.
  • dc.contributor.author Pérez, Yolanda
  • dc.contributor.author Martínez, Javier P.
  • dc.contributor.author Barnadas Rodríguez, Ramón
  • dc.contributor.author Schultz, Anke
  • dc.contributor.author von Briesen, Hagen
  • dc.contributor.author Perálvarez Marín, Alex
  • dc.contributor.author Meyerhans, Andreas
  • dc.contributor.author Haro, Isabel
  • dc.date.accessioned 2019-03-26T09:37:44Z
  • dc.date.available 2019-03-26T09:37:44Z
  • dc.date.issued 2019
  • dc.description.abstract 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.
  • dc.description.sponsorship 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). The 500 MHz spectrometer was purchased in part through a Research Infrastructure MINECO-FEDER fund (Grant CSIC13-4E-2076). Partial financial support from the Spanish National Research Council (CSIC) is also gratefully acknowledged.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Gomara MJ, Perez Y, Martinez JP, Barnadas-Rodriguez R, Schultz A, von Briesen H et al. Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides. Sci Rep. 2019;9(1):3257. DOI: 10.1038/s41598-019-40125-4
  • dc.identifier.doi http://dx.doi.org/10.1038/s41598-019-40125-4
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/36962
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Scientific Reports. 2019;9(1):3257
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-75505-R
  • dc.rights © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Membrane biophysics
  • dc.subject.keyword Peptides
  • dc.title Peptide assembly on the membrane determines the HIV-1 inhibitory activity of dual-targeting fusion inhibitor peptides
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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