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Targeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugates

2022Artigo científico Acesso aberto
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dc.contributor.authorTodorovski, Toni
dc.contributor.authorMendonça, Diogo A.
dc.contributor.authorFernandes-Siqueira, Lorena O.
dc.contributor.authorCruz-Oliveira, Christine
dc.contributor.authorGuida, Giuseppina
dc.contributor.authorValle, Javier
dc.contributor.authorCavaco, Marco
dc.contributor.authorLimas, Fernanda I. V.
dc.contributor.authorNeves, Vera
dc.contributor.authorCadima Couto, Carla Iris
dc.contributor.authorDefaus, Sira
dc.contributor.authorVeiga, Ana Salomé
dc.contributor.authorDa Poian, Andrea T.
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorAndreu, David
dc.date.accessioned2023-05-24T13:40:24Z
dc.date.available2023-05-24T13:40:24Z
dc.date.issued2022
dc.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/).pt_PT
dc.description.abstractViral 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.pt_PT
dc.description.sponsorshipWork 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPharmaceutics 2022, 14, 738pt_PT
dc.identifier.doi10.3390/pharmaceutics14040738pt_PT
dc.identifier.eissn1999-4923
dc.identifier.urihttp://hdl.handle.net/10451/57575
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationPTDC/BIAVIR/29495/2017pt_PT
dc.relation''One size fits all'' unique drug to eradicate multiple viral species simultaneously from the central nervous system of co-infected individuals
dc.relationTargeting brain-resident viruses across the blood-brain barrier using peptide drugs.
dc.relationTrans-BBB peptides for targeting brain metastasis
dc.relation.publisherversionhttps://www.mdpi.com/journal/pharmaceuticspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectPeptide-drug conjugatespt_PT
dc.subjectBlood–brain barrierpt_PT
dc.subjectBlood–placental barrierpt_PT
dc.subjectZika viruspt_PT
dc.subjectBBB shuttlespt_PT
dc.subjectPorphyrinspt_PT
dc.subjectAntiviralspt_PT
dc.titleTargeting Zika virus with new brain- and placenta-crossing peptide–porphyrin conjugatespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitle''One size fits all'' unique drug to eradicate multiple viral species simultaneously from the central nervous system of co-infected individuals
oaire.awardTitleTargeting brain-resident viruses across the blood-brain barrier using peptide drugs.
oaire.awardTitleTrans-BBB peptides for targeting brain metastasis
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/828774/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F136752%2F2018/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F128281%2F2017/PT
oaire.citation.issue4pt_PT
oaire.citation.startPage738pt_PT
oaire.citation.titlePharmaceuticspt_PT
oaire.citation.volume14pt_PT
oaire.fundingStreamH2020
oaire.fundingStreamOE
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project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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