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

Detalhes bibliográficos
Autor(a) principal: Fontinha, Diana
Data de Publicação: 2022
Outros Autores: Arez, Francisca, Gal, Isabella Ramella, Nogueira, Gonçalo, Moita, Diana, Baeurle, Tobias Hyun Ho, Brito, Catarina, Spangenberg, Thomas, Alves, Paula M., Prudêncio, Miguel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/52526
Resumo: Copyright © 2022 The Authors. Published by American Chemical Society
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spelling Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection modelsM5717Combination therapyDrug discoveryLiver stage infectionMalariaPyronaridineCopyright © 2022 The Authors. Published by American Chemical SocietyCombination 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.This 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.ACS PublicationsRepositório da Universidade de LisboaFontinha, DianaArez, FranciscaGal, Isabella RamellaNogueira, GonçaloMoita, DianaBaeurle, Tobias Hyun HoBrito, CatarinaSpangenberg, ThomasAlves, Paula M.Prudêncio, Miguel2022-04-21T16:08:51Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/52526engACS Infect Dis. 2022 Apr 8;8(4):721-72710.1021/acsinfecdis.1c006402373-8227info: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:RCAAP2023-11-08T16:57:46Zoai:repositorio.ul.pt:10451/52526Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:03:36.568182Repositório 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 Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection models
title Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection models
spellingShingle Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection models
Fontinha, Diana
M5717
Combination therapy
Drug discovery
Liver stage infection
Malaria
Pyronaridine
title_short Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection models
title_full Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection models
title_fullStr Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection models
title_full_unstemmed Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection models
title_sort Pre-erythrocytic activity of M5717 in monotherapy and combination in preclinical Plasmodium infection models
author Fontinha, Diana
author_facet Fontinha, Diana
Arez, Francisca
Gal, Isabella Ramella
Nogueira, Gonçalo
Moita, Diana
Baeurle, Tobias Hyun Ho
Brito, Catarina
Spangenberg, Thomas
Alves, Paula M.
Prudêncio, Miguel
author_role author
author2 Arez, Francisca
Gal, Isabella Ramella
Nogueira, Gonçalo
Moita, Diana
Baeurle, Tobias Hyun Ho
Brito, Catarina
Spangenberg, Thomas
Alves, Paula M.
Prudêncio, Miguel
author2_role 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 Fontinha, Diana
Arez, Francisca
Gal, Isabella Ramella
Nogueira, Gonçalo
Moita, Diana
Baeurle, Tobias Hyun Ho
Brito, Catarina
Spangenberg, Thomas
Alves, Paula M.
Prudêncio, Miguel
dc.subject.por.fl_str_mv M5717
Combination therapy
Drug discovery
Liver stage infection
Malaria
Pyronaridine
topic M5717
Combination therapy
Drug discovery
Liver stage infection
Malaria
Pyronaridine
description Copyright © 2022 The Authors. Published by American Chemical Society
publishDate 2022
dc.date.none.fl_str_mv 2022-04-21T16:08:51Z
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/52526
url http://hdl.handle.net/10451/52526
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv ACS Infect Dis. 2022 Apr 8;8(4):721-727
10.1021/acsinfecdis.1c00640
2373-8227
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv ACS Publications
publisher.none.fl_str_mv ACS Publications
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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