Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library

Detalhes bibliográficos
Autor(a) principal: Pascoalino, Bruno S.
Data de Publicação: 2016
Outros Autores: Courtemanche, Gilles, Cordeiro, Marli T., Gil, Laura H. V. G., Freitas-Junior, Lucio
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/18829
Resumo: Centro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brazil / Instituto Butantan. São Paulo, SP, Brazil.
id CRUZ_802cbe75556f108796b916ba5d07779a
oai_identifier_str oai:www.arca.fiocruz.br:icict/18829
network_acronym_str CRUZ
network_name_str Repositório Institucional da FIOCRUZ (ARCA)
repository_id_str 2135
spelling Pascoalino, Bruno S.Courtemanche, GillesCordeiro, Marli T.Gil, Laura H. V. G.Freitas-Junior, Lucio2017-05-11T17:39:32Z2017-05-11T17:39:32Z2016PASCOALINO, B. S. et al. Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library. F1000Research, v. 5, p. 2523, 14 out. 2016.2046-1402https://www.arca.fiocruz.br/handle/icict/1882910.12688/f1000research.9648.1engZika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved libraryinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCentro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brazil / Instituto Butantan. São Paulo, SP, Brazil.BIOASTER. Paris, France.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Fundação Oswaldo Cruz. Instituto Aggeu Magalhães. Recife, PE, Brasil.Centro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brazil / Instituto Butantan. São Paulo, SP, Brazil.Background The recent epidemics of Zika virus (ZIKV) implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the Guillain-Barré syndrome in otherwise healthy patients. Recent findings showed that anti-Dengue antibodies are capable of amplifying ZIKV infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. This scenario becomes potentially catastrophic when the global burden of Dengue and the advent of the newly approved anti-Dengue vaccines in the near future are taken into account. Thus, antiviral chemotherapy should be pursued as a priority strategy to control the spread of the virus and prevent the complications associated with Zika. Methods Here we describe a fast and reliable cell-based, high-content screening assay for discovery of anti-ZIKV compounds. This methodology has been used to screen the National Institute of Health Clinical Collection compound library, a small collection of FDA-approved drugs. Results and conclusion From 725 FDA-approved compounds triaged, 29 (4%) were found to have anti-Zika virus activity, of which 22 had confirmed (76% of confirmation) by dose-response curves. Five candidates presented selective activity against ZIKV infection and replication in a human cell line. These hits have abroad spectrum of chemotypes and therapeutic uses, offering valuable opportunities for selection of leads for antiviral drug discovery.FDA-approved drugsHigh content screening drug discoveryZikainfo: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/18829/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINAL27909576 2016 pas-zik.pdf27909576 2016 pas-zik.pdfapplication/pdf4873876https://www.arca.fiocruz.br/bitstream/icict/18829/2/27909576%202016%20pas-zik.pdf69eb4a73b3e93bb76910afeeda15c7a7MD52TEXT27909576 2016 pas-zik.pdf.txt27909576 2016 pas-zik.pdf.txtExtracted texttext/plain58848https://www.arca.fiocruz.br/bitstream/icict/18829/3/27909576%202016%20pas-zik.pdf.txt87ad7240ab6d88badbd997b78faa81b9MD53icict/188292019-04-02 17:04:30.971oai:www.arca.fiocruz.br:icict/18829Q0VTU8ODTyBOw4NPIEVYQ0xVU0lWQSBERSBESVJFSVRPUyBBVVRPUkFJUwoKQW8gYWNlaXRhciBvcyBURVJNT1MgZSBDT05EScOHw5VFUyBkZXN0YSBDRVNTw4NPLCBvIEFVVE9SIGUvb3UgVElUVUxBUiBkZSBkaXJlaXRvcwphdXRvcmFpcyBzb2JyZSBhIE9CUkEgZGUgcXVlIHRyYXRhIGVzdGUgZG9jdW1lbnRvOgoKKDEpIENFREUgZSBUUkFOU0ZFUkUsIHRvdGFsIGUgZ3JhdHVpdGFtZW50ZSwgw6AgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaLCBlbQpjYXLDoXRlciBwZXJtYW5lbnRlLCBpcnJldm9nw6F2ZWwgZSBOw4NPIEVYQ0xVU0lWTywgdG9kb3Mgb3MgZGlyZWl0b3MgcGF0cmltb25pYWlzIE7Dg08KQ09NRVJDSUFJUyBkZSB1dGlsaXphw6fDo28gZGEgT0JSQSBhcnTDrXN0aWNhIGUvb3UgY2llbnTDrWZpY2EgaW5kaWNhZGEgYWNpbWEsIGluY2x1c2l2ZSBvcyBkaXJlaXRvcwpkZSB2b3ogZSBpbWFnZW0gdmluY3VsYWRvcyDDoCBPQlJBLCBkdXJhbnRlIHRvZG8gbyBwcmF6byBkZSBkdXJhw6fDo28gZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCBlbQpxdWFscXVlciBpZGlvbWEgZSBlbSB0b2RvcyBvcyBwYcOtc2VzOwoKKDIpIEFDRUlUQSBxdWUgYSBjZXNzw6NvIHRvdGFsIG7Do28gZXhjbHVzaXZhLCBwZXJtYW5lbnRlIGUgaXJyZXZvZ8OhdmVsIGRvcyBkaXJlaXRvcyBhdXRvcmFpcwpwYXRyaW1vbmlhaXMgbsOjbyBjb21lcmNpYWlzIGRlIHV0aWxpemHDp8OjbyBkZSBxdWUgdHJhdGEgZXN0ZSBkb2N1bWVudG8gaW5jbHVpLCBleGVtcGxpZmljYXRpdmFtZW50ZSwKb3MgZGlyZWl0b3MgZGUgZGlzcG9uaWJpbGl6YcOnw6NvIGUgY29tdW5pY2HDp8OjbyBww7pibGljYSBkYSBPQlJBLCBlbSBxdWFscXVlciBtZWlvIG91IHZlw61jdWxvLAppbmNsdXNpdmUgZW0gUmVwb3NpdMOzcmlvcyBEaWdpdGFpcywgYmVtIGNvbW8gb3MgZGlyZWl0b3MgZGUgcmVwcm9kdcOnw6NvLCBleGliacOnw6NvLCBleGVjdcOnw6NvLApkZWNsYW1hw6fDo28sIHJlY2l0YcOnw6NvLCBleHBvc2nDp8OjbywgYXJxdWl2YW1lbnRvLCBpbmNsdXPDo28gZW0gYmFuY28gZGUgZGFkb3MsIHByZXNlcnZhw6fDo28sIGRpZnVzw6NvLApkaXN0cmlidWnDp8OjbywgZGl2dWxnYcOnw6NvLCBlbXByw6lzdGltbywgdHJhZHXDp8OjbywgZHVibGFnZW0sIGxlZ2VuZGFnZW0sIGluY2x1c8OjbyBlbSBub3ZhcyBvYnJhcyBvdQpjb2xldMOibmVhcywgcmV1dGlsaXphw6fDo28sIGVkacOnw6NvLCBwcm9kdcOnw6NvIGRlIG1hdGVyaWFsIGRpZMOhdGljbyBlIGN1cnNvcyBvdSBxdWFscXVlciBmb3JtYSBkZQp1dGlsaXphw6fDo28gbsOjbyBjb21lcmNpYWw7CgooMykgUkVDT05IRUNFIHF1ZSBhIGNlc3PDo28gYXF1aSBlc3BlY2lmaWNhZGEgY29uY2VkZSDDoCBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPCkNSVVogbyBkaXJlaXRvIGRlIGF1dG9yaXphciBxdWFscXVlciBwZXNzb2Eg4oCTIGbDrXNpY2Egb3UganVyw61kaWNhLCBww7pibGljYSBvdSBwcml2YWRhLCBuYWNpb25hbCBvdQplc3RyYW5nZWlyYSDigJMgYSBhY2Vzc2FyIGUgdXRpbGl6YXIgYW1wbGFtZW50ZSBhIE9CUkEsIHNlbSBleGNsdXNpdmlkYWRlLCBwYXJhIHF1YWlzcXVlcgpmaW5hbGlkYWRlcyBuw6NvIGNvbWVyY2lhaXM7CgooNCkgREVDTEFSQSBxdWUgYSBvYnJhIMOpIGNyaWHDp8OjbyBvcmlnaW5hbCBlIHF1ZSDDqSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGFxdWkgY2VkaWRvcyBlIGF1dG9yaXphZG9zLApyZXNwb25zYWJpbGl6YW5kby1zZSBpbnRlZ3JhbG1lbnRlIHBlbG8gY29udGXDumRvIGUgb3V0cm9zIGVsZW1lbnRvcyBxdWUgZmF6ZW0gcGFydGUgZGEgT0JSQSwKaW5jbHVzaXZlIG9zIGRpcmVpdG9zIGRlIHZveiBlIGltYWdlbSB2aW5jdWxhZG9zIMOgIE9CUkEsIG9icmlnYW5kby1zZSBhIGluZGVuaXphciB0ZXJjZWlyb3MgcG9yCmRhbm9zLCBiZW0gY29tbyBpbmRlbml6YXIgZSByZXNzYXJjaXIgYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVogZGUKZXZlbnR1YWlzIGRlc3Blc2FzIHF1ZSB2aWVyZW0gYSBzdXBvcnRhciwgZW0gcmF6w6NvIGRlIHF1YWxxdWVyIG9mZW5zYSBhIGRpcmVpdG9zIGF1dG9yYWlzIG91CmRpcmVpdG9zIGRlIHZveiBvdSBpbWFnZW0sIHByaW5jaXBhbG1lbnRlIG5vIHF1ZSBkaXogcmVzcGVpdG8gYSBwbMOhZ2lvIGUgdmlvbGHDp8O1ZXMgZGUgZGlyZWl0b3M7CgooNSkgQUZJUk1BIHF1ZSBjb25oZWNlIGEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTwpPU1dBTERPIENSVVogZSBhcyBkaXJldHJpemVzIHBhcmEgbyBmdW5jaW9uYW1lbnRvIGRvIHJlcG9zaXTDs3JpbyBpbnN0aXR1Y2lvbmFsIEFSQ0EuCgpBIFBvbMOtdGljYSBJbnN0aXR1Y2lvbmFsIGRlIEFjZXNzbyBBYmVydG8gZGEgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaIHJlc2VydmEKZXhjbHVzaXZhbWVudGUgYW8gQVVUT1Igb3MgZGlyZWl0b3MgbW9yYWlzIGUgb3MgdXNvcyBjb21lcmNpYWlzIHNvYnJlIGFzIG9icmFzIGRlIHN1YSBhdXRvcmlhCmUvb3UgdGl0dWxhcmlkYWRlLCBzZW5kbyBvcyB0ZXJjZWlyb3MgdXN1w6FyaW9zIHJlc3BvbnPDoXZlaXMgcGVsYSBhdHJpYnVpw6fDo28gZGUgYXV0b3JpYSBlIG1hbnV0ZW7Dp8OjbwpkYSBpbnRlZ3JpZGFkZSBkYSBPQlJBIGVtIHF1YWxxdWVyIHV0aWxpemHDp8Ojby4KCkEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVoKcmVzcGVpdGEgb3MgY29udHJhdG9zIGUgYWNvcmRvcyBwcmVleGlzdGVudGVzIGRvcyBBdXRvcmVzIGNvbSB0ZXJjZWlyb3MsIGNhYmVuZG8gYW9zIEF1dG9yZXMKaW5mb3JtYXIgw6AgSW5zdGl0dWnDp8OjbyBhcyBjb25kacOnw7VlcyBlIG91dHJhcyByZXN0cmnDp8O1ZXMgaW1wb3N0YXMgcG9yIGVzdGVzIGluc3RydW1lbnRvcy4KRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-04-02T20:04:30Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library
title Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library
spellingShingle Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library
Pascoalino, Bruno S.
FDA-approved drugs
High content screening drug discovery
Zika
title_short Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library
title_full Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library
title_fullStr Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library
title_full_unstemmed Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library
title_sort Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library
author Pascoalino, Bruno S.
author_facet Pascoalino, Bruno S.
Courtemanche, Gilles
Cordeiro, Marli T.
Gil, Laura H. V. G.
Freitas-Junior, Lucio
author_role author
author2 Courtemanche, Gilles
Cordeiro, Marli T.
Gil, Laura H. V. G.
Freitas-Junior, Lucio
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Pascoalino, Bruno S.
Courtemanche, Gilles
Cordeiro, Marli T.
Gil, Laura H. V. G.
Freitas-Junior, Lucio
dc.subject.en.none.fl_str_mv FDA-approved drugs
High content screening drug discovery
Zika
topic FDA-approved drugs
High content screening drug discovery
Zika
description Centro Nacional de Pesquisa em Energia e Materiais. Laboratório Nacional de Biociências. Campinas, SP, Brazil / Instituto Butantan. São Paulo, SP, Brazil.
publishDate 2016
dc.date.issued.fl_str_mv 2016
dc.date.accessioned.fl_str_mv 2017-05-11T17:39:32Z
dc.date.available.fl_str_mv 2017-05-11T17:39:32Z
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 PASCOALINO, B. S. et al. Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library. F1000Research, v. 5, p. 2523, 14 out. 2016.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/18829
dc.identifier.issn.pt_BR.fl_str_mv 2046-1402
dc.identifier.doi.pt_BR.fl_str_mv 10.12688/f1000research.9648.1
identifier_str_mv PASCOALINO, B. S. et al. Zika antiviral chemotherapy: identification of drugs and promising starting points for drug discovery from an FDA-approved library. F1000Research, v. 5, p. 2523, 14 out. 2016.
2046-1402
10.12688/f1000research.9648.1
url https://www.arca.fiocruz.br/handle/icict/18829
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.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/18829/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/18829/2/27909576%202016%20pas-zik.pdf
https://www.arca.fiocruz.br/bitstream/icict/18829/3/27909576%202016%20pas-zik.pdf.txt
bitstream.checksum.fl_str_mv 5a560609d32a3863062d77ff32785d58
69eb4a73b3e93bb76910afeeda15c7a7
87ad7240ab6d88badbd997b78faa81b9
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_ 1798324935798554624

Registros relacionados