Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides

Detalhes bibliográficos
Autor(a) principal: Mathieu, Cyrille
Data de Publicação: 2017
Outros Autores: Augusto, Marcelo T., Niewiesk, Stefan, Horvat, Branka, Palermo, Laura M., Sanna, Giuseppina, Madeddu, Silvia, Huey, Devra, Castanho, Miguel A. R. B., Porotto, Matteo, Santos, Nuno C., Moscona, Anne
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/33890
Resumo: © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
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spelling Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides© The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Human paramyxoviruses include global causes of lower respiratory disease like the parainfluenza viruses, as well as agents of lethal encephalitis like Nipah virus. Infection is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. Paramyxovirus viral fusion proteins (F) insert into the target cell membrane, and form a transient intermediate that pulls the viral and cell membranes together as two heptad-repeat regions refold to form a six-helix bundle structure that can be specifically targeted by fusion-inhibitory peptides. Antiviral potency can be improved by sequence modification and lipid conjugation, and by adding linkers between the protein and lipid components. We exploit the uniquely broad spectrum antiviral activity of a parainfluenza F-derived peptide sequence that inhibits both parainfluenza and Nipah viruses, to investigate the influence of peptide orientation and intervening linker length on the peptides' interaction with transitional states of F, solubility, membrane insertion kinetics, and protease sensitivity. We assessed the impact of these features on biodistribution and antiviral efficacy in vitro and in vivo. The engineering approach based on biophysical parameters resulted in a peptide that is a highly effective inhibitor of both paramyxoviruses and a set of criteria to be used for engineering broad spectrum antivirals for emerging paramyxoviruses.This research was funded by NIH grants RO1AI114736, R33AI101333, and RO1AI031971 to A.M. and by ANRASTRID-2011. M.T.A. has fellowship support SFRH/BD/95624/2013 from Fundação para a Ciência e Tecnologia - Ministério da Educação e Ciência (FCT-MEC, Portugal) and support from Fundação Luso Americana para o Desenvolvimento (FLAD) Proj. 4/2016. We thank Peter Collins and Alex Bukreyev (National Institutes for Allergy and Infectious Diseases, National Institutes of Health, USA) for the recombinant HPIV3 expressing enhanced GFP.Nature Publishing GroupRepositório da Universidade de LisboaMathieu, CyrilleAugusto, Marcelo T.Niewiesk, StefanHorvat, BrankaPalermo, Laura M.Sanna, GiuseppinaMadeddu, SilviaHuey, DevraCastanho, Miguel A. R. B.Porotto, MatteoSantos, Nuno C.Moscona, Anne2018-06-12T08:43:58Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/33890engScientific Reports volume 7, Article number: 43610 (2017)2045-232210.1038/srep43610info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:28:46Zoai:repositorio.ul.pt:10451/33890Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:48:41.312232Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides
title Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides
spellingShingle Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides
Mathieu, Cyrille
title_short Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides
title_full Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides
title_fullStr Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides
title_full_unstemmed Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides
title_sort Broad spectrum antiviral activity for paramyxoviruses is modulated by biophysical properties of fusion inhibitory peptides
author Mathieu, Cyrille
author_facet Mathieu, Cyrille
Augusto, Marcelo T.
Niewiesk, Stefan
Horvat, Branka
Palermo, Laura M.
Sanna, Giuseppina
Madeddu, Silvia
Huey, Devra
Castanho, Miguel A. R. B.
Porotto, Matteo
Santos, Nuno C.
Moscona, Anne
author_role author
author2 Augusto, Marcelo T.
Niewiesk, Stefan
Horvat, Branka
Palermo, Laura M.
Sanna, Giuseppina
Madeddu, Silvia
Huey, Devra
Castanho, Miguel A. R. B.
Porotto, Matteo
Santos, Nuno C.
Moscona, Anne
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Mathieu, Cyrille
Augusto, Marcelo T.
Niewiesk, Stefan
Horvat, Branka
Palermo, Laura M.
Sanna, Giuseppina
Madeddu, Silvia
Huey, Devra
Castanho, Miguel A. R. B.
Porotto, Matteo
Santos, Nuno C.
Moscona, Anne
description © The Author(s) 2017. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01T00:00:00Z
2018-06-12T08:43:58Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/33890
url http://hdl.handle.net/10451/33890
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Scientific Reports volume 7, Article number: 43610 (2017)
2045-2322
10.1038/srep43610
dc.rights.driver.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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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