Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents

Detalhes bibliográficos
Autor(a) principal: Giuliani, Sandra
Data de Publicação: 2018
Outros Autores: Silva, Arthur de Carvalho, Borba, Joyce Villa Verde Borba, Ramos, Pablo Ivan Pereira, Paveley, Ross A, Muratov, Eugene N, Andrade, Carolina Horta, Furnham, Nicholas
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/30592
Resumo: Medical Research Council (MRC; https://mrc.ukri.org) Research Methodology Fellowship (MRC: MR/K020420). CHA thanks Brazilian funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; http://www.cnpq.br), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; http://www.capes.gov.br) and Goias Research Support Foundation (FAPEG; Fapeg.go. gov.br) for financial support and fellowships. ACS and JVVBB are supported by CAPES fellowships. ENM appreciates support from National Institutes of Health (NIH; https://www.nih.gov) (grant 1U01CA207160) and CNPq (grant 400760/2014- 2). CHA is CNPq research fellow and supported by “L’Ore´al-UNESCO-ABC Para Mulheres na Ciência” and “L’Oréal-UNESCO International Rising Talents” (https://www.forwomeninscience.com/en/home).
id CRUZ_be534ca6d74362fb3e4a6555fab3eae7
oai_identifier_str oai:www.arca.fiocruz.br:icict/30592
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Giuliani, SandraSilva, Arthur de CarvalhoBorba, Joyce Villa Verde BorbaRamos, Pablo Ivan PereiraPaveley, Ross AMuratov, Eugene NAndrade, Carolina HortaFurnham, Nicholas2018-12-14T12:47:24Z2018-12-14T12:47:24Z2018GIULIANI, S. et al. Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents. PLoS Computational Biology, v. 14, n. 10, p. e1006515, 2018.1553-734Xhttps://www.arca.fiocruz.br/handle/icict/3059210.1371/journal.pcbi.1006515Medical Research Council (MRC; https://mrc.ukri.org) Research Methodology Fellowship (MRC: MR/K020420). CHA thanks Brazilian funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; http://www.cnpq.br), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; http://www.capes.gov.br) and Goias Research Support Foundation (FAPEG; Fapeg.go. gov.br) for financial support and fellowships. ACS and JVVBB are supported by CAPES fellowships. ENM appreciates support from National Institutes of Health (NIH; https://www.nih.gov) (grant 1U01CA207160) and CNPq (grant 400760/2014- 2). CHA is CNPq research fellow and supported by “L’Ore´al-UNESCO-ABC Para Mulheres na Ciência” and “L’Oréal-UNESCO International Rising Talents” (https://www.forwomeninscience.com/en/home).London School of Hygiene and Tropical Medicine. Department of Pathogen Molecular Biology. London, United Kingdom.Universidade Federal de Goiás. Faculdade de Farmácia. Laboratory for Molecular Modeling and Drug Design. Goiânia, Goiás, Brasil.Universidade Federal de Goiás. Faculdade de Farmácia. Laboratory for Molecular Modeling and Drug Design. Goiânia, Goiás, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilLondon School of Hygiene and Tropical Medicine. Department of Pathogen Molecular Biology. London, United Kingdom.University of North Carolina. Division of Chemical Biology and Medicinal Chemistry. Laboratory for Molecular Modeling. Chapel Hill, NC, United States of America / Odessa National Polytechnic University. Department of Chemical Technology. Odessa, Ukraine.Universidade Federal de Goiás. Faculdade de Farmácia. Laboratory for Molecular Modeling and Drug Design. Goiânia, Goiás, Brasil / University of Campinas. Institute of Biology. Department of Genetics, Evolution, Microbiology and Immunology, Laboratory of Tropical Diseasesampinas. São Paulo, SP, Brazil.London School of Hygiene and Tropical Medicine. Department of Pathogen Molecular Biology. London, United Kingdom.The development of novel therapeutics is urgently required for diseases where existing treatments are failing due to the emergence of resistance. This is particularly pertinent for parasitic infections of the tropics and sub-tropics, referred to collectively as neglected tropical diseases, where the commercial incentives to develop new drugs are weak. One such disease is schistosomiasis, a highly prevalent acute and chronic condition caused by a parasitic helminth infection, with three species of the genus Schistosoma infecting humans. Currently, a single 40-year old drug, praziquantel, is available to treat all infective species, but its use in mass drug administration is leading to signs of drug-resistance emerging. To meet the challenge of developing new therapeutics against this disease, we developed an innovative computational drug repurposing pipeline supported by phenotypic screening. The approach highlighted several protein kinases as interesting new biological targets for schistosomiasis as they play an essential role in many parasite's biological processes. Focusing on this target class, we also report the first elucidation of the kinome of Schistosoma japonicum, as well as updated kinomes of S. mansoni and S. haematobium. In comparison with the human kinome, we explored these kinomes to identify potential targets of existing inhibitors which are unique to Schistosoma species, allowing us to identify novel targets and suggest approved drugs that might inhibit them. These include previously suggested schistosomicidal agents such as bosutinib, dasatinib, and imatinib as well as new inhibitors such as vandetanib, saracatinib, tideglusib, alvocidib, dinaciclib, and 22 newly identified targets such as CHK1, CDC2, WEE, PAKA, MEK1. Additionally, the primary and secondary targets in Schistosoma of those approved drugs are also suggested, allowing for the development of novel therapeutics against this important yet neglected disease.engPublic Library of ScienceDrogasQuinaseEsquistossomicidasEsquistossomoseSchistosoma mansoniResistencia a drogasHumanosDrugKinaseSchistosomicidesSchistosomiasisSchistosoma mansoniDrug ResistanceHumansComputationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agentsinfo: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/30592/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALGiuliani S. Computationally-guided...2018.pdfGiuliani S. Computationally-guided...2018.pdfapplication/pdf2779949https://www.arca.fiocruz.br/bitstream/icict/30592/2/Giuliani%20S.%20Computationally-guided...2018.pdf0e6b6d4ec4071eea8cd3a8e929484bb7MD52TEXTGiuliani S. Computationally-guided...2018.pdf.txtGiuliani S. Computationally-guided...2018.pdf.txtExtracted texttext/plain75471https://www.arca.fiocruz.br/bitstream/icict/30592/3/Giuliani%20S.%20Computationally-guided...2018.pdf.txt1ca8bd7686bc434d31ce2fc70599d7adMD53icict/305922023-03-15 14:34:15.737oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-03-15T17:34:15Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents
title Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents
spellingShingle Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents
Giuliani, Sandra
Drogas
Quinase
Esquistossomicidas
Esquistossomose
Schistosoma mansoni
Resistencia a drogas
Humanos
Drug
Kinase
Schistosomicides
Schistosomiasis
Schistosoma mansoni
Drug Resistance
Humans
title_short Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents
title_full Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents
title_fullStr Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents
title_full_unstemmed Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents
title_sort Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents
author Giuliani, Sandra
author_facet Giuliani, Sandra
Silva, Arthur de Carvalho
Borba, Joyce Villa Verde Borba
Ramos, Pablo Ivan Pereira
Paveley, Ross A
Muratov, Eugene N
Andrade, Carolina Horta
Furnham, Nicholas
author_role author
author2 Silva, Arthur de Carvalho
Borba, Joyce Villa Verde Borba
Ramos, Pablo Ivan Pereira
Paveley, Ross A
Muratov, Eugene N
Andrade, Carolina Horta
Furnham, Nicholas
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Giuliani, Sandra
Silva, Arthur de Carvalho
Borba, Joyce Villa Verde Borba
Ramos, Pablo Ivan Pereira
Paveley, Ross A
Muratov, Eugene N
Andrade, Carolina Horta
Furnham, Nicholas
dc.subject.other.pt_BR.fl_str_mv Drogas
Quinase
Esquistossomicidas
Esquistossomose
Schistosoma mansoni
Resistencia a drogas
Humanos
topic Drogas
Quinase
Esquistossomicidas
Esquistossomose
Schistosoma mansoni
Resistencia a drogas
Humanos
Drug
Kinase
Schistosomicides
Schistosomiasis
Schistosoma mansoni
Drug Resistance
Humans
dc.subject.en.pt_BR.fl_str_mv Drug
Kinase
Schistosomicides
Schistosomiasis
Schistosoma mansoni
Drug Resistance
Humans
description Medical Research Council (MRC; https://mrc.ukri.org) Research Methodology Fellowship (MRC: MR/K020420). CHA thanks Brazilian funding agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; http://www.cnpq.br), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; http://www.capes.gov.br) and Goias Research Support Foundation (FAPEG; Fapeg.go. gov.br) for financial support and fellowships. ACS and JVVBB are supported by CAPES fellowships. ENM appreciates support from National Institutes of Health (NIH; https://www.nih.gov) (grant 1U01CA207160) and CNPq (grant 400760/2014- 2). CHA is CNPq research fellow and supported by “L’Ore´al-UNESCO-ABC Para Mulheres na Ciência” and “L’Oréal-UNESCO International Rising Talents” (https://www.forwomeninscience.com/en/home).
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-12-14T12:47:24Z
dc.date.available.fl_str_mv 2018-12-14T12:47:24Z
dc.date.issued.fl_str_mv 2018
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.citation.fl_str_mv GIULIANI, S. et al. Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents. PLoS Computational Biology, v. 14, n. 10, p. e1006515, 2018.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/30592
dc.identifier.issn.pt_BR.fl_str_mv 1553-734X
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pcbi.1006515
identifier_str_mv GIULIANI, S. et al. Computationally-guided drug repurposing enables the discovery of kinase targets and inhibitors as new schistosomicidal agents. PLoS Computational Biology, v. 14, n. 10, p. e1006515, 2018.
1553-734X
10.1371/journal.pcbi.1006515
url https://www.arca.fiocruz.br/handle/icict/30592
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/30592/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/30592/2/Giuliani%20S.%20Computationally-guided...2018.pdf
https://www.arca.fiocruz.br/bitstream/icict/30592/3/Giuliani%20S.%20Computationally-guided...2018.pdf.txt
bitstream.checksum.fl_str_mv 5a560609d32a3863062d77ff32785d58
0e6b6d4ec4071eea8cd3a8e929484bb7
1ca8bd7686bc434d31ce2fc70599d7ad
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
_version_ 1798324609838219264

Registros relacionados