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Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection models

2022Artigo científico Acesso aberto
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dc.contributor.authorFontinha, Diana
dc.contributor.authorArez, Francisca
dc.contributor.authorGal, Isabella Ramella
dc.contributor.authorNogueira, Gonçalo
dc.contributor.authorMoita, Diana
dc.contributor.authorBaeurle, Tobias Hyun Ho
dc.contributor.authorBrito, Catarina
dc.contributor.authorSpangenberg, Thomas
dc.contributor.authorAlves, Paula M.
dc.contributor.authorPrudêncio, Miguel
dc.date.accessioned2022-04-21T16:08:51Z
dc.date.available2022-04-21T16:08:51Z
dc.date.issued2022
dc.descriptionCopyright © 2022 The Authors. Published by American Chemical Societypt_PT
dc.description.abstractCombination therapies have emerged to mitigate Plasmodium drug resistance, which has hampered the fight against malaria. M5717 is a potent multistage antiplasmodial drug under clinical development, which inhibits parasite protein synthesis. The combination of M5717 with pyronaridine, an inhibitor of hemozoin formation, displays potent activity against blood stage Plasmodium infection. However, the impact of this therapy on liver infection by Plasmodium remains unknown. Here, we employed a recently described 3D culture-based hepatic infection platform to evaluate the activity of the M5717-pyronaridine combination against hepatic infection by P. berghei. This effect was further confirmed in vivo by employing the C57BL/6J rodent Plasmodium infection model. Collectively, our data demonstrate that pyronaridine potentiates the activity of M5717 against P. berghei hepatic development. These preclinical results contribute to the validation of pyronaridine as a suitable partner drug for M5717, supporting the clinical evaluation of this novel antiplasmodial combination therapy.pt_PT
dc.description.sponsorshipThis work was funded by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). M.P. is a recipient of a “Concurso de Estímulo ao Emprego Científico” Principal Investigator award of Fundação para a Ciência e Tecnologia, Portugal (FCT), with ref. N. CEECIND/03539/2017. D.F. is funded by FCT project CRCNA/BRB/0281/2019. F.A. is recipient of a PhD fellowship PD/BD/128371/2017, funded by FCT.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationACS Infect Dis. 2022 Apr 8;8(4):721-727pt_PT
dc.identifier.doi10.1021/acsinfecdis.1c00640pt_PT
dc.identifier.eissn2373-8227
dc.identifier.urihttp://hdl.handle.net/10451/52526
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherACS Publicationspt_PT
dc.relationNot Available
dc.relationAMAZING – AMAZonian snake toxins: creatING value from bioresources
dc.relationNovel Cel-based platform for drug screening targeting plasmodium hepatic infection
dc.relation.publisherversionhttps://pubs.acs.org/journal/aidcbcpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectM5717pt_PT
dc.subjectCombination therapypt_PT
dc.subjectDrug discoverypt_PT
dc.subjectLiver stage infectionpt_PT
dc.subjectMalariapt_PT
dc.subjectPyronaridinept_PT
dc.titlePre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection modelspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleNot Available
oaire.awardTitleAMAZING – AMAZonian snake toxins: creatING value from bioresources
oaire.awardTitleNovel Cel-based platform for drug screening targeting plasmodium hepatic infection
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/CEEC IND 2017/CEECIND%2F03539%2F2017%2FCP1396%2FCT0009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/CIRCNA%2FBRB%2F0281%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F128371%2F2017/PT
oaire.citation.endPage727pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage721pt_PT
oaire.citation.titleACS Infectious Diseasespt_PT
oaire.citation.volume8pt_PT
oaire.fundingStreamCEEC IND 2017
oaire.fundingStream3599-PPCDT
oaire.fundingStreamOE
person.familyNameFontinha
person.familyNameNogueira Seabra Pereira
person.familyNameAlves Moita
person.familyNamePrudêncio
person.givenNameDiana
person.givenNameLuciano Gonçalo
person.givenNameDiana
person.givenNameMiguel
person.identifierhttps://scholar.google.pt/citations?user=zduN6wsAAAAJ&hl=pt-PT&oi=ao
person.identifier.ciencia-id6A17-C404-F33B
person.identifier.ciencia-id7E19-6243-016A
person.identifier.ciencia-idFC1B-A174-8DFD
person.identifier.ciencia-id5511-16ED-48E0
person.identifier.orcid0000-0002-0046-648X
person.identifier.orcid0000-0003-3836-6246
person.identifier.orcid0000-0002-7958-8630
person.identifier.orcid0000-0003-1746-6029
person.identifier.scopus-author-id6603561872
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
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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