Publicação
Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membrane
| Resumo: | The impact of influenza virus infection is felt each year on a global scale when approximately 5−10% of adults and 20−30% of children globally are infected. While vaccination is the primary strategy for influenza prevention, there are a number of likely scenarios for which vaccination is inadequate, making the development of effective antiviral agents of utmost importance. Anti-influenza treatments with innovative mechanisms of action are critical in the face of emerging viral resistance to the existing drugs. These new antiviral agents are urgently needed to address future epidemic (or pandemic) influenza and are critical for the immune-compromised cohort who cannot be vaccinated. We have previously shown that lipid tagged peptides derived from the C-terminal region of influenza hemagglutinin (HA) were effective influenza fusion inhibitors. In this study, we modified the influenza fusion inhibitors by adding a cell penetrating peptide sequence to promote intracellular targeting. These fusion-inhibiting peptides self-assemble into ∼15−30 nm nanoparticles (NPs), target relevant infectious tissues in vivo, and reduce viral infectivity upon interaction with the cell membrane. Overall, our data show that the CPP and the lipid moiety are both required for efficient biodistribution, fusion inhibition, and efficacy in vivo. |
|---|---|
| Autores principais: | Figueira, Tiago Nascimento |
| Outros Autores: | Augusto, Marcelo Tavares; Rybkina, K.; Stelitano, D.; Noval, M. G.; Harder, O. E.; Veiga, Ana Salome; Huey, D.; Alabi, C. A.; Biswas, S.; Niewiesk, S.; Moscona, A.; Santos, Nuno C.; Castanho, Miguel A. R. B.; Porotto, M. |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso restrito |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1866810084059774976 |
|---|---|
| author | Figueira, Tiago Nascimento |
| author2 | Augusto, Marcelo Tavares Rybkina, K. Stelitano, D. Noval, M. G. Harder, O. E. Veiga, Ana Salome Huey, D. Alabi, C. A. Biswas, S. Niewiesk, S. Moscona, A. Santos, Nuno C. Castanho, Miguel A. R. B. Porotto, M. |
| author2_role | author author author author author author author author author author author author author author |
| author_facet | Figueira, Tiago Nascimento Augusto, Marcelo Tavares Rybkina, K. Stelitano, D. Noval, M. G. Harder, O. E. Veiga, Ana Salome Huey, D. Alabi, C. A. Biswas, S. Niewiesk, S. Moscona, A. Santos, Nuno C. Castanho, Miguel A. R. B. Porotto, M. |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Figueira, Tiago Nascimento\",\"Person.identifier.orcid\":\"0000-0002-0813-0745\"},{\"Person.name\":\"Augusto, Marcelo Tavares\"},{\"Person.name\":\"Rybkina, K.\"},{\"Person.name\":\"Stelitano, D.\"},{\"Person.name\":\"Noval, M. G.\"},{\"Person.name\":\"Harder, O. E.\"},{\"Person.name\":\"Veiga, Ana Salome\",\"Person.identifier.orcid\":\"0000-0002-9892-2243\"},{\"Person.name\":\"Huey, D.\"},{\"Person.name\":\"Alabi, C. A.\"},{\"Person.name\":\"Biswas, S.\"},{\"Person.name\":\"Niewiesk, S.\"},{\"Person.name\":\"Moscona, A.\"},{\"Person.name\":\"Santos, Nuno C.\",\"Person.identifier.orcid\":\"0000-0002-0580-0475\"},{\"Person.name\":\"Castanho, Miguel A. R. B.\",\"Person.identifier.orcid\":\"0000-0001-7891-7562\"},{\"Person.name\":\"Porotto, M.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Figueira, Tiago Nascimento Augusto, Marcelo Tavares Rybkina, K. Stelitano, D. Noval, M. G. Harder, O. E. Veiga, Ana Salome Huey, D. Alabi, C. A. Biswas, S. Niewiesk, S. Moscona, A. Santos, Nuno C. Castanho, Miguel A. R. B. Porotto, M. |
| datacite.date.Accepted.fl_str_mv | 2018-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2019-03-22T12:28:57Z |
| datacite.date.embargoed.fl_str_mv | 2019-03-22T12:28:57Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| datacite.titles.title.fl_str_mv | Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membrane |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Figueira, Tiago Nascimento Augusto, Marcelo Tavares Rybkina, K. Stelitano, D. Noval, M. G. Harder, O. E. Veiga, Ana Salome Huey, D. Alabi, C. A. Biswas, S. Niewiesk, S. Moscona, A. Santos, Nuno C. Castanho, Miguel A. R. B. Porotto, M. |
| dc.date.Accepted.fl_str_mv | 2018-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2019-03-22T12:28:57Z |
| dc.date.embargoed.fl_str_mv | 2019-03-22T12:28:57Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/37658 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | American Chemical Society |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_16ec |
| dc.title.fl_str_mv | Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membrane |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| description | The impact of influenza virus infection is felt each year on a global scale when approximately 5−10% of adults and 20−30% of children globally are infected. While vaccination is the primary strategy for influenza prevention, there are a number of likely scenarios for which vaccination is inadequate, making the development of effective antiviral agents of utmost importance. Anti-influenza treatments with innovative mechanisms of action are critical in the face of emerging viral resistance to the existing drugs. These new antiviral agents are urgently needed to address future epidemic (or pandemic) influenza and are critical for the immune-compromised cohort who cannot be vaccinated. We have previously shown that lipid tagged peptides derived from the C-terminal region of influenza hemagglutinin (HA) were effective influenza fusion inhibitors. In this study, we modified the influenza fusion inhibitors by adding a cell penetrating peptide sequence to promote intracellular targeting. These fusion-inhibiting peptides self-assemble into ∼15−30 nm nanoparticles (NPs), target relevant infectious tissues in vivo, and reduce viral infectivity upon interaction with the cell membrane. Overall, our data show that the CPP and the lipid moiety are both required for efficient biodistribution, fusion inhibition, and efficacy in vivo. |
| dirty | 0 |
| eu_rights_str_mv | restrictedAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/a379f10e-3425-4b2a-b8f2-ba76b5fd2ba2/download |
| funding.funder.alternateName_str_mv | FCT FCT |
| funding.funder.identifier_str_mv | http://doi.org/10.13039/501100001871 http://doi.org/10.13039/501100001871 |
| funding.funder.name_str_mv | Fundação para a Ciência e a Tecnologia Fundação para a Ciência e a Tecnologia |
| funding.name_str_mv | 3599-PPCDT 3599-PPCDT |
| id | ul_89a728c99a2c19c8a3c4bbf06f38439f |
| identifier.url.fl_str_mv | http://hdl.handle.net/10451/37658 |
| instacron_str | ul |
| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
| network_acronym_str | ul |
| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/37658 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Figueira, Tiago Nascimento Figueira, Tiago Nascimento http://orcid.org/0000-0002-0813-0745 0000-0002-0813-0745 Augusto, Marcelo Tavares Rybkina, K. Stelitano, D. Noval, M. G. Harder, O. E. Veiga, Ana Salome Veiga, Ana Salome http://orcid.org/0000-0002-9892-2243 0000-0002-9892-2243 Huey, D. Alabi, C. A. Biswas, S. Niewiesk, S. Moscona, A. Santos, Nuno C. Santos, Nuno C. https://www.ciencia-id.pt/CD13-5E3A-A3C5 CD13-5E3A-A3C5 http://orcid.org/0000-0002-0580-0475 0000-0002-0580-0475 Castanho, Miguel A. R. B. Castanho, Miguel A. R. B. http://orcid.org/0000-0001-7891-7562 0000-0001-7891-7562 Porotto, M. |
| publishDate | 2018 |
| publisher.none.fl_str_mv | American Chemical Society |
| reponame_str | Repositório da Universidade de Lisboa |
| repository_id_str | urn:repositoryAcronym:ul |
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| spelling | engAmerican Chemical Societypt_PTThe impact of influenza virus infection is felt each year on a global scale when approximately 5−10% of adults and 20−30% of children globally are infected. While vaccination is the primary strategy for influenza prevention, there are a number of likely scenarios for which vaccination is inadequate, making the development of effective antiviral agents of utmost importance. Anti-influenza treatments with innovative mechanisms of action are critical in the face of emerging viral resistance to the existing drugs. These new antiviral agents are urgently needed to address future epidemic (or pandemic) influenza and are critical for the immune-compromised cohort who cannot be vaccinated. We have previously shown that lipid tagged peptides derived from the C-terminal region of influenza hemagglutinin (HA) were effective influenza fusion inhibitors. In this study, we modified the influenza fusion inhibitors by adding a cell penetrating peptide sequence to promote intracellular targeting. These fusion-inhibiting peptides self-assemble into ∼15−30 nm nanoparticles (NPs), target relevant infectious tissues in vivo, and reduce viral infectivity upon interaction with the cell membrane. Overall, our data show that the CPP and the lipid moiety are both required for efficient biodistribution, fusion inhibition, and efficacy in vivo.application/pdfpt_PTEffective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membranePersonalFigueira, Tiago NascimentoDSpacehttp://dspace.org/items/c65d67d4-bb09-45c4-be75-376e1f048665DSpacehttp://dspace.org/items/c65d67d4-bb09-45c4-be75-376e1f048665FigueiraTiagoORCIDhttp://orcid.org0000-0002-0813-0745Augusto, Marcelo TavaresRybkina, K.Stelitano, D.Noval, M. G.Harder, O. E.PersonalVeiga, Ana SalomeDSpacehttp://dspace.org/items/e4303354-5eaa-4d48-8198-de1adc9beb19DSpacehttp://dspace.org/items/e4303354-5eaa-4d48-8198-de1adc9beb19VeigaAna SalomeORCIDhttp://orcid.org0000-0002-9892-2243Scopus Author IDhttps://www.scopus.com56745037100Huey, D.Alabi, C. A.Biswas, S.Niewiesk, S.Moscona, A.PersonalSantos, Nuno C.DSpacehttp://dspace.org/items/4656d912-5a2d-4c80-8921-2bcba3aa441aDSpacehttp://dspace.org/items/4656d912-5a2d-4c80-8921-2bcba3aa441aSantosNunoCiência IDhttps://www.ciencia-id.ptCD13-5E3A-A3C5ORCIDhttp://orcid.org0000-0002-0580-0475Researcher IDhttps://www.researcherid.comN-7248-2013Scopus Author IDhttps://www.scopus.com55940818300PersonalCastanho, Miguel A. R. B.DSpacehttp://dspace.org/items/f5e46f85-fabf-450a-9ee2-1c7b59410892DSpacehttp://dspace.org/items/f5e46f85-fabf-450a-9ee2-1c7b59410892CastanhoMiguelORCIDhttp://orcid.org0000-0001-7891-7562Scopus Author IDhttps://www.scopus.com56605575600Porotto, M.HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptISSNIsPartOf1043-1802DOIIsPartOf10.1021/acs.bioconjchem.8b005272019-03-22T12:28:57Z20182018-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/37658http://purl.org/coar/access_right/c_16ecrestricted access6043038 bytesFundação para a Ciência e a TecnologiaTowards the development of innovative highly effective dual action anti-HIV peptides3599-PPCDTCrossref Funder IDhttp://doi.org/10.13039/501100001871Fundação para a Ciência e a TecnologiaBroad-spectrum antiviral peptides against respiratory viruses3599-PPCDTCrossref Funder IDhttp://doi.org/10.13039/501100001871literaturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_16ecapplication/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/a379f10e-3425-4b2a-b8f2-ba76b5fd2ba2/downloadBioconjugate Chemistry2933623376 |
| spellingShingle | Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membrane Figueira, Tiago Nascimento |
| status | SINGLETON |
| title | Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membrane |
| title_full | Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membrane |
| title_fullStr | Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membrane |
| title_full_unstemmed | Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membrane |
| title_short | Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membrane |
| title_sort | Effective in vivo targeting of influenza virus through a cell-penetrating/fusion inhibitor tandem peptide anchored to the plasma membrane |
| url | http://hdl.handle.net/10451/37658 |
| visible | 1 |