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Repurposing anti-cancer porphyrin derivative drugs to target SARS-CoV-2 envelope

2024-05-17Artigo científico Acesso aberto
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dc.contributor.authorMendonça, Diogo A.
dc.contributor.authorCadima Couto, Carla Iris
dc.contributor.authorBuga, Carolina C.
dc.contributor.authorArnaut, Zoe A.
dc.contributor.authorSchaberle, Fabio A.
dc.contributor.authorArnaut, Luis G.
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorCruz-Oliveira, Christine
dc.date.accessioned2025-02-06T15:13:36Z
dc.date.available2025-02-06T15:13:36Z
dc.date.issued2024-05-17
dc.description© 2024 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).pt_PT
dc.description.abstractAntiviral medicines to treat COVID-19 are still scarce. Porphyrins and porphyrin derivatives (PDs) usually present broad-spectrum antiviral activity with low risk of resistance development. In fact, some PDs are clinicall approved to be used in anti-cancer photodynamic therapy and repurposing clinically approved PDs might be an alternative to treat COVID-19. Here, we characterize the ability of temoporfin, verteporfin, talaporfin and redaporfin to inactivate SARS-CoV-2 infectious particles. PDs light-dependent and –independent effect on SARSCoV-2 infectivity were evaluated. PDs photoactivation successfully inactivated SARS-CoV-2 with very low concentrations and light dose. However, only temoporfin and verteporfin inactivated SARS-CoV-2 in the dark, being verteporfin the most effective. PDs treatment reduced viral load in infected Caco-2 cells, while not inducing cytotoxicity. Furthermore, light-independent treatment with temoporfin and verteporfin act on early stages of viral infection. Using lipid vehicles as membrane models, we characterized PDs interaction to the viral envelope. Verteporfin presented the lowest IC50 for viral inactivation and the highest partition coefficients (Kp) towards lipid bilayers. Curiously, although temoporfin and redaporfin presented similar Kps, redaporfin did not present light-independent antiviral activity, and only temoporfin and verteporfin caused lipid membrane disorder. In fact, redaporfin is located closer to the bilayer surface, while temoporfin and verteporfin are located closer to the centre. Our results suggest that viral envelope affinity, with penetration and destabilization of the lipid bilayer, seems critical to mediate PDs antiviral activity. Altogether, these findings open new avenues for the off-label application of temoporfin and verteporfin in the systemic treatment of COVID-19.pt_PT
dc.description.sponsorshipThis project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 828774 and Fundação para a Ciência e a Tecnologia, I.P., through project RESEARCH4COVID n◦ 470, MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020), LS4FUTURE Associated Laboratory (LA/P/0087/2020) and iNOVA4Health R&D Unit (UIDB/ 04462/2020, UIDP/04462/2020). Additional funding from Fundação para a Ciência e a Tecnologia, I.P. is also acknowledged for D.A.M. (PD/ BD/136752/2018); ´I.C.-C. (PTDC/BIAVIR/29495/2017); C.C.B. (2022.13959.BD); Z.A.A (2021.09454.BD); FAS (PTDC/QUI -OUT/ 0303/2021).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBiomedicine & Pharmacotherapy 176 (2024) 116768pt_PT
dc.identifier.doi10.1016/j.biopha.2024.116768pt_PT
dc.identifier.eissn1950-6007
dc.identifier.issn0753-3322
dc.identifier.urihttp://hdl.handle.net/10400.5/98171
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_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.relationLife Sciences for a Healthy and Sustainable Future
dc.relationSelecting anti-Zika virus drug leads able to translocate the blood-placental and blood-brain barriers. Combining innovative and effective translocating peptides with new antivirals to target Zika across barriers.
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/biomedicine-and-pharmacotherapypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectSARS-CoV-2pt_PT
dc.subjectAntiviral agentspt_PT
dc.subjectPorphyrin derivativespt_PT
dc.subjectVerteporfinpt_PT
dc.subjectTemoporfinpt_PT
dc.subjectMembrane targetingpt_PT
dc.titleRepurposing anti-cancer porphyrin derivative drugs to target SARS-CoV-2 envelopept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumber828774
oaire.awardNumberUIDB/04612/2020
oaire.awardNumberUIDP/04612/2020
oaire.awardNumberLA/P/0087/2020
oaire.awardNumberUIDB/04462/2020
oaire.awardNumberUIDP/04462/2020
oaire.awardNumberPD/BD/136752/2018
oaire.awardNumberPTDC/BIA-VIR/29495/2017
oaire.awardNumber2022.13959.BD
oaire.awardNumber2021.09454.BD
oaire.awardNumberPTDC/QUI-OUT/0303/2021
oaire.awardTitle''One size fits all'' unique drug to eradicate multiple viral species simultaneously from the central nervous system of co-infected individuals
oaire.awardTitleLife Sciences for a Healthy and Sustainable Future
oaire.awardTitleSelecting anti-Zika virus drug leads able to translocate the blood-placental and blood-brain barriers. Combining innovative and effective translocating peptides with new antivirals to target Zika across barriers.
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/828774/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Base/UIDB%2F04612%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Programático/UIDP%2F04612%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0087%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Base/UIDB%2F04462%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017%2F2018) - Financiamento Programático/UIDP%2F04462%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F136752%2F2018/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2017/PTDC%2FBIA-VIR%2F29495%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//2022.13959.BD/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POR_CENTRO/2021.09454.BD/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FQUI-OUT%2F0303%2F2021/PT
oaire.citation.issue176pt_PT
oaire.citation.startPage116768pt_PT
oaire.citation.titleBiomedicine & Pharmacotherapypt_PT
oaire.fundingStreamH2020
oaire.fundingStreamConcurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Base
oaire.fundingStreamConcurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Programático
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamConcurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Base
oaire.fundingStreamConcurso de avaliação no âmbito do Programa Plurianual de Financiamento de Unidades de I&D (2017/2018) - Financiamento Programático
oaire.fundingStreamConcurso para Financiamento de Projetos de Investigação Científica e Desenvolvimento Tecnológico em Todos os Domínios Científicos - 2017
oaire.fundingStreamPOR_CENTRO
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