Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates
| Autor(a) principal: | |
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| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/57575 |
Resumo: | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
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Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugatesPeptide-drug conjugatesBlood–brain barrierBlood–placental barrierZika virusBBB shuttlesPorphyrinsAntivirals© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Viral disease outbreaks affect hundreds of millions of people worldwide and remain a serious threat to global health. The current SARS-CoV-2 pandemic and other recent geographically-confined viral outbreaks (severe acute respiratory syndrome (SARS), Ebola, dengue, zika and ever-recurring seasonal influenza), also with devastating tolls at sanitary and socio-economic levels, are sobering reminders in this respect. Among the respective pathogenic agents, Zika virus (ZIKV), transmitted by Aedes mosquito vectors and causing the eponymous fever, is particularly insidious in that infection during pregnancy results in complications such as foetal loss, preterm birth or irreversible brain abnormalities, including microcephaly. So far, there is no effective remedy for ZIKV infection, mainly due to the limited ability of antiviral drugs to cross blood–placental and/or blood–brain barriers (BPB and BBB, respectively). Despite its restricted permeability, the BBB is penetrable by a variety of molecules, mainly peptide-based, and named BBB peptide shuttles (BBBpS), able to ferry various payloads (e.g., drugs, antibodies, etc.) into the brain. Recently, we have described peptide–porphyrin conjugates (PPCs) as successful BBBpS-associated drug leads for HIV, an enveloped virus in which group ZIKV also belongs. Herein, we report on several brain-directed, low-toxicity PPCs capable of targeting ZIKV. One of the conjugates, PP-P1, crossing both BPB and BBB, has shown to be effective against ZIKV (IC50 1.08 µM) and has high serum stability (t1/2 ca. 22 h) without altering cell viability at all tested concentrations. Peptide–porphyrin conjugation stands out as a promising strategy to fill the ZIKV treatment gap.Work supported by the La Caixa Health Foundation (project HR17_00409, ID 100010434, agreement LCF/PR/HR17/52150011) and by the European Union (H2020-FETOPEN-2018-2019-2020-01 grant no 828774). The Department of Medicine and Life Sciences, Pompeu Fabra University, belongs to the María de Maeztu network of Units of Excellence, funded by the Spanish MICINNand AEI (CEX2018-000792-M). Additional funding from Fundação para a Ciência e Tecnologia (FCT-MCTES) is also acknowledged for D.A.M. (PD/BD/136752/2018), M.C. (PD/BD/128281/2017), and for C.C.-O. and Í.C.-C. (PTDC/BIAVIR/29495/2017). The grants from Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Brazil (grant numbers 201.316/2016, 202.945/2017); and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil (grant number 309028/2017-5) are also acknowledged.MDPIRepositório da Universidade de LisboaTodorovski, ToniMendonça, Diogo A.Fernandes-Siqueira, Lorena O.Cruz-Oliveira, ChristineGuida, GiuseppinaValle, JavierCavaco, MarcoLimas, Fernanda I. V.Neves, VeraCadima Couto, Carla IrisDefaus, SiraVeiga, Ana SaloméDa Poian, Andrea T.Castanho, Miguel A. R. B.Andreu, David2023-05-24T13:40:24Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/57575engPharmaceutics 2022, 14, 73810.3390/pharmaceutics140407381999-4923info: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:RCAAP2023-11-08T17:06:05Zoai:repositorio.ul.pt:10451/57575Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:08:02.125321Repositório 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 |
Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates |
| title |
Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates |
| spellingShingle |
Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates Todorovski, Toni Peptide-drug conjugates Blood–brain barrier Blood–placental barrier Zika virus BBB shuttles Porphyrins Antivirals |
| title_short |
Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates |
| title_full |
Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates |
| title_fullStr |
Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates |
| title_full_unstemmed |
Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates |
| title_sort |
Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates |
| author |
Todorovski, Toni |
| author_facet |
Todorovski, Toni Mendonça, Diogo A. Fernandes-Siqueira, Lorena O. Cruz-Oliveira, Christine Guida, Giuseppina Valle, Javier Cavaco, Marco Limas, Fernanda I. V. Neves, Vera Cadima Couto, Carla Iris Defaus, Sira Veiga, Ana Salomé Da Poian, Andrea T. Castanho, Miguel A. R. B. Andreu, David |
| author_role |
author |
| author2 |
Mendonça, Diogo A. Fernandes-Siqueira, Lorena O. Cruz-Oliveira, Christine Guida, Giuseppina Valle, Javier Cavaco, Marco Limas, Fernanda I. V. Neves, Vera Cadima Couto, Carla Iris Defaus, Sira Veiga, Ana Salomé Da Poian, Andrea T. Castanho, Miguel A. R. B. Andreu, David |
| author2_role |
author author author 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 |
Todorovski, Toni Mendonça, Diogo A. Fernandes-Siqueira, Lorena O. Cruz-Oliveira, Christine Guida, Giuseppina Valle, Javier Cavaco, Marco Limas, Fernanda I. V. Neves, Vera Cadima Couto, Carla Iris Defaus, Sira Veiga, Ana Salomé Da Poian, Andrea T. Castanho, Miguel A. R. B. Andreu, David |
| dc.subject.por.fl_str_mv |
Peptide-drug conjugates Blood–brain barrier Blood–placental barrier Zika virus BBB shuttles Porphyrins Antivirals |
| topic |
Peptide-drug conjugates Blood–brain barrier Blood–placental barrier Zika virus BBB shuttles Porphyrins Antivirals |
| description |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2022-01-01T00:00:00Z 2023-05-24T13:40:24Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/57575 |
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http://hdl.handle.net/10451/57575 |
| dc.language.iso.fl_str_mv |
eng |
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eng |
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Pharmaceutics 2022, 14, 738 10.3390/pharmaceutics14040738 1999-4923 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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MDPI |
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MDPI |
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