Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds

Detalhes bibliográficos
Autor(a) principal: Borba, Joyce Villa Verde Bastos
Data de Publicação: 2019
Outros Autores: Silva, Arthur C., Ramos, Pablo Ivan Pereira, Grazzia, Nathalia, Miguel, Danilo Ciccone, Muratov, Eugene N., Furnham, Nicholas, Andrade, Carolina Horta
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/32426
Resumo: CNPq, CAPES, and FAPEG for fellowships and funding this work. E.N.M. appreciate support from NIH (grant 1U01CA207160) and CNPq (grant 400760/2014-2). NF is supported by the Medical Research Council (grantMR/K020420/1). DCM is a recipient of a young investigator award from FAPESP (2014/21129-4). CHA has a research fellow in productivity of CNPq. CHA also thanks the “L'Oréal-UNESCOABC Para Mulheres na Ciência” and “L'Oréal-UNESCO International Rising Talents” for the awards and fellowships received, which partially funded thiswork. Additionally, JVBB and ACSwere supported by fellowships from CAPES.
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spelling Borba, Joyce Villa Verde BastosSilva, Arthur C.Ramos, Pablo Ivan PereiraGrazzia, NathaliaMiguel, Danilo CicconeMuratov, Eugene N.Furnham, NicholasAndrade, Carolina Horta2019-04-09T16:40:32Z2019-04-09T16:40:32Z2019BORBA, Joyce Villa Verde Bastos et al. Unveiling the kinomes of Leishmania infantum and L. braziliensis empowers the discovery of new kinase targets and antileishmanial compounds. Computational and Structural Biotechnology Journal, v. 17, p. 352–361, 2019.2001-0370https://www.arca.fiocruz.br/handle/icict/3242610.1016/j.csbj.2019.02.005CNPq, CAPES, and FAPEG for fellowships and funding this work. E.N.M. appreciate support from NIH (grant 1U01CA207160) and CNPq (grant 400760/2014-2). NF is supported by the Medical Research Council (grantMR/K020420/1). DCM is a recipient of a young investigator award from FAPESP (2014/21129-4). CHA has a research fellow in productivity of CNPq. CHA also thanks the “L'Oréal-UNESCOABC Para Mulheres na Ciência” and “L'Oréal-UNESCO International Rising Talents” for the awards and fellowships received, which partially funded thiswork. Additionally, JVBB and ACSwere supported by fellowships from CAPES.Universidade Federal de Goiás. Faculdade de Farmácia. Laboratory for Molecular Modeling and Drug Design. Goiânia, GO, Brasil.Universidade Federal de Goiás. Faculdade de Farmácia. Laboratory for Molecular Modeling and Drug Design. Goiânia, GO, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.State University of Campinas. Biology Institute. Laboratory of Leishmania Biology Infection Studies. Department of Animal Biology. Campinas, SP, Brasil.State University of Campinas. Biology Institute. Laboratory of Leishmania Biology Infection Studies. Department of Animal Biology. Campinas, SP, Brasil.University of North Carolina. Eshelman School of Pharmacy. Laboratory for Molecular Modeling. Division of Chemical Biology and Medicinal Chemistry. Chapel Hill, NC, USA / Odessa National Polytechnic University. Department of Chemical Technology. Odessa, Ukraine.London School of Hygiene and Tropical Medicine. Department of Pathogen Molecular Biology. London, UK.Universidade Federal de Goiás. Faculdade de Farmácia. Laboratory for Molecular Modeling and Drug Design. Goiânia, GO, Brasil.Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania (NTD) endemic in 98 countries. Although some drugs are available, current treatments deal with issues such as toxicity, low efficacy, and emergence of resistance. Therefore, there is an urgent need to identify new targets for the development of new antileishmanial drugs. Protein kinases (PKs), which play an essential role in many biological processes, have become potential drug targets for many parasitic diseases. A refined bioinformatics pipeline was applied in order to define and compare the kinomes of L. infantum and L. braziliensis, species that cause cutaneous and visceral manifestations of leishmaniasis in the Americas, the latter being potentially fatal if untreated. Respectively, 224 and 221 PKs were identified in L. infantum and L. braziliensis overall. Almost all unclassified eukaryotic PKs were assigned to six of nine major kinase groups and, consequently, most have been classified into family and subfamily. Furthermore, revealing the kinomes for both Leishmania species allowed for the prioritization of potential drug targets that could be explored for discovering new drugs against leishmaniasis. Finally, we used a drug repurposing approach and prioritized seven approved drugs and investigational compounds to be experimentally tested against Leishmania. Trametinib and NMS-1286937 inhibited the growth of L. infantum and L. braziliensis promastigotes and amastigotes and therefore might be good candidates for the drug repurposing pipeline.engElsevierLeishmania infantumLeishmania braziliensisKinomeQuinasesReaproveitamento de drogasPriorização de metasLeishmania infantumLeishmania braziliensisKinomeKinasesDrug repurposingTarget prioritizationUnveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compoundsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/32426/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALBorba J. Unveiling the kinomes...2019.pdfBorba J. Unveiling the kinomes...2019.pdfapplication/pdf604364https://www.arca.fiocruz.br/bitstream/icict/32426/2/Borba%20J.%20Unveiling%20the%20kinomes...2019.pdfbc42a4406b1398d770853cd73c27becfMD52TEXTBorba J. Unveiling the kinomes...2019.pdf.txtBorba J. 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dc.title.pt_BR.fl_str_mv Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds
title Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds
spellingShingle Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds
Borba, Joyce Villa Verde Bastos
Leishmania infantum
Leishmania braziliensis
Kinome
Quinases
Reaproveitamento de drogas
Priorização de metas
Leishmania infantum
Leishmania braziliensis
Kinome
Kinases
Drug repurposing
Target prioritization
title_short Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds
title_full Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds
title_fullStr Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds
title_full_unstemmed Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds
title_sort Unveiling the Kinomes of Leishmania infantum and L. braziliensis Empowers the Discovery of New Kinase Targets and Antileishmanial Compounds
author Borba, Joyce Villa Verde Bastos
author_facet Borba, Joyce Villa Verde Bastos
Silva, Arthur C.
Ramos, Pablo Ivan Pereira
Grazzia, Nathalia
Miguel, Danilo Ciccone
Muratov, Eugene N.
Furnham, Nicholas
Andrade, Carolina Horta
author_role author
author2 Silva, Arthur C.
Ramos, Pablo Ivan Pereira
Grazzia, Nathalia
Miguel, Danilo Ciccone
Muratov, Eugene N.
Furnham, Nicholas
Andrade, Carolina Horta
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Borba, Joyce Villa Verde Bastos
Silva, Arthur C.
Ramos, Pablo Ivan Pereira
Grazzia, Nathalia
Miguel, Danilo Ciccone
Muratov, Eugene N.
Furnham, Nicholas
Andrade, Carolina Horta
dc.subject.other.pt_BR.fl_str_mv Leishmania infantum
Leishmania braziliensis
Kinome
Quinases
Reaproveitamento de drogas
Priorização de metas
topic Leishmania infantum
Leishmania braziliensis
Kinome
Quinases
Reaproveitamento de drogas
Priorização de metas
Leishmania infantum
Leishmania braziliensis
Kinome
Kinases
Drug repurposing
Target prioritization
dc.subject.en.pt_BR.fl_str_mv Leishmania infantum
Leishmania braziliensis
Kinome
Kinases
Drug repurposing
Target prioritization
description CNPq, CAPES, and FAPEG for fellowships and funding this work. E.N.M. appreciate support from NIH (grant 1U01CA207160) and CNPq (grant 400760/2014-2). NF is supported by the Medical Research Council (grantMR/K020420/1). DCM is a recipient of a young investigator award from FAPESP (2014/21129-4). CHA has a research fellow in productivity of CNPq. CHA also thanks the “L'Oréal-UNESCOABC Para Mulheres na Ciência” and “L'Oréal-UNESCO International Rising Talents” for the awards and fellowships received, which partially funded thiswork. Additionally, JVBB and ACSwere supported by fellowships from CAPES.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-04-09T16:40:32Z
dc.date.available.fl_str_mv 2019-04-09T16:40:32Z
dc.date.issued.fl_str_mv 2019
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.citation.fl_str_mv BORBA, Joyce Villa Verde Bastos et al. Unveiling the kinomes of Leishmania infantum and L. braziliensis empowers the discovery of new kinase targets and antileishmanial compounds. Computational and Structural Biotechnology Journal, v. 17, p. 352–361, 2019.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/32426
dc.identifier.issn.pt_BR.fl_str_mv 2001-0370
dc.identifier.doi.none.fl_str_mv 10.1016/j.csbj.2019.02.005
identifier_str_mv BORBA, Joyce Villa Verde Bastos et al. Unveiling the kinomes of Leishmania infantum and L. braziliensis empowers the discovery of new kinase targets and antileishmanial compounds. Computational and Structural Biotechnology Journal, v. 17, p. 352–361, 2019.
2001-0370
10.1016/j.csbj.2019.02.005
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