Desenvolvimento de antivirais: Triagem de inibidores da protease do vírus Zika
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/11600/67220 |
Resumo: | O crescente surgimento e ressurgimento mundial de doenças virais tornou o desenvolvimento de novos antivirais extremamente importante. No caso do vírus Zika, vários surtos importantes foram relatados desde sua primeira identificação em 1947, incluindo o surto de Zika entre 2015-2016. Como a protease do vírus Zika é um alvo essencial e bem estabelecido para o desenvolvimento de agentes antivirais, este trabalho teve como objetivo realizar uma varredura bioquímica de pequenos compostos utilizando uma forma recombinante desta enzima. Como resultado, foi possível identificar 12 inibidores de protease do vírus Zika. Esses compostos são todos produtos naturais e apresentaram forte inibição nos ensaios bioquímicos. Os valores das constantes inibitórias (Ki) para os compostos variaram de 5 nM a 8 μM. Entre os inibidores mais potentes estão alguns flavonóides como o irigenol hexa-acetato (1, Ki = 0,28 μM), katacina (2, Ki = 0,26 μM) e teaflavina galato (5, Ki = 0,40 μM). Os inibidores de outros grupos de produtos naturais incluem senosídeo A (9, Ki = 0,19 μM) e gossipol (10, Ki = 0,70 μM). Vários dos compostos obtidos são conhecidos pelos seus efeitos benéficos para a saúde humana. Portanto, eles podem constituir compostos líderes relevantes para o desenvolvimento de futuros medicamentos antivirais contra o Zika. |
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Coelho, Camila de Morais [UNIFESP]http://lattes.cnpq.br/2584731188791527http://lattes.cnpq.br/0625673643875019Würtele, Martin [UNIFESP]São José dos Campos, SP2023-03-10T14:28:50Z2023-03-10T14:28:50Z2022-12-08https://repositorio.unifesp.br/11600/67220O crescente surgimento e ressurgimento mundial de doenças virais tornou o desenvolvimento de novos antivirais extremamente importante. No caso do vírus Zika, vários surtos importantes foram relatados desde sua primeira identificação em 1947, incluindo o surto de Zika entre 2015-2016. Como a protease do vírus Zika é um alvo essencial e bem estabelecido para o desenvolvimento de agentes antivirais, este trabalho teve como objetivo realizar uma varredura bioquímica de pequenos compostos utilizando uma forma recombinante desta enzima. Como resultado, foi possível identificar 12 inibidores de protease do vírus Zika. Esses compostos são todos produtos naturais e apresentaram forte inibição nos ensaios bioquímicos. Os valores das constantes inibitórias (Ki) para os compostos variaram de 5 nM a 8 μM. Entre os inibidores mais potentes estão alguns flavonóides como o irigenol hexa-acetato (1, Ki = 0,28 μM), katacina (2, Ki = 0,26 μM) e teaflavina galato (5, Ki = 0,40 μM). Os inibidores de outros grupos de produtos naturais incluem senosídeo A (9, Ki = 0,19 μM) e gossipol (10, Ki = 0,70 μM). Vários dos compostos obtidos são conhecidos pelos seus efeitos benéficos para a saúde humana. Portanto, eles podem constituir compostos líderes relevantes para o desenvolvimento de futuros medicamentos antivirais contra o Zika.The worldwide emergence and re-emergence of viral diseases of great global impact has made the development of new antivirals paramount. In the case of the Zika virus, several major outbreaks have been reported since its first identification in 1947. This includes the 2015-2016 Zika outbreak. As the Zika virus protease is an essential and well-established target for the development of antiviral agents against Zika, in this work, inhibitors were biochemically screened using a recombinantly expressed form of this enzyme. As a result, 12 potent Zika virus protease inhibitors were identified. These compounds are all natural products. They showed strong inhibition in the biochemical assays, with inhibitory constants (Ki) values for the compounds ranging from 5 nM to 8 μM. Among the most potent inhibitors are flavonoids like irigenol hexa-acetate (1, Ki= 0.28 μM), katacine (2, Ki= 0.26 μM) and theaflavin gallate (5, Ki= 0.40 μM). Inhibitors from other groups of natural products include sennoside A (9, Ki= 0.19 μM) and gossypol (10, Ki= 0.70 μM). Several of the obtained compounds are known for their beneficial health effects. Thus, they could be of interest as lead compounds for the development of important and essential Zika antiviral drugs.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)88882.431004/2019-0176 f.porUniversidade Federal de São PauloZikaproteaseinibidorvarredura bioquímicaDesenvolvimento de antivirais: Triagem de inibidores da protease do vírus Zikainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPInstituto de Ciência e Tecnologia (ICT)BiotecnologiaBioquímica e Biologia EstruturalLICENSElicense.txtlicense.txttext/plain; charset=utf-85826${dspace.ui.url}/bitstream/11600/67220/2/license.txtd5b3ed3107d0e07ea7ecbfa2d2c9f636MD52open accessORIGINALTese_CamilaCoelho_s (1).pdfTese_CamilaCoelho_s 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InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-10-31T04:00:35Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.pt_BR.fl_str_mv |
Desenvolvimento de antivirais: Triagem de inibidores da protease do vírus Zika |
title |
Desenvolvimento de antivirais: Triagem de inibidores da protease do vírus Zika |
spellingShingle |
Desenvolvimento de antivirais: Triagem de inibidores da protease do vírus Zika Coelho, Camila de Morais [UNIFESP] Zika protease inibidor varredura bioquímica |
title_short |
Desenvolvimento de antivirais: Triagem de inibidores da protease do vírus Zika |
title_full |
Desenvolvimento de antivirais: Triagem de inibidores da protease do vírus Zika |
title_fullStr |
Desenvolvimento de antivirais: Triagem de inibidores da protease do vírus Zika |
title_full_unstemmed |
Desenvolvimento de antivirais: Triagem de inibidores da protease do vírus Zika |
title_sort |
Desenvolvimento de antivirais: Triagem de inibidores da protease do vírus Zika |
author |
Coelho, Camila de Morais [UNIFESP] |
author_facet |
Coelho, Camila de Morais [UNIFESP] |
author_role |
author |
dc.contributor.authorLattes.pt_BR.fl_str_mv |
http://lattes.cnpq.br/2584731188791527 |
dc.contributor.advisorLattes.pt_BR.fl_str_mv |
http://lattes.cnpq.br/0625673643875019 |
dc.contributor.author.fl_str_mv |
Coelho, Camila de Morais [UNIFESP] |
dc.contributor.advisor1.fl_str_mv |
Würtele, Martin [UNIFESP] |
contributor_str_mv |
Würtele, Martin [UNIFESP] |
dc.subject.por.fl_str_mv |
Zika protease inibidor varredura bioquímica |
topic |
Zika protease inibidor varredura bioquímica |
description |
O crescente surgimento e ressurgimento mundial de doenças virais tornou o desenvolvimento de novos antivirais extremamente importante. No caso do vírus Zika, vários surtos importantes foram relatados desde sua primeira identificação em 1947, incluindo o surto de Zika entre 2015-2016. Como a protease do vírus Zika é um alvo essencial e bem estabelecido para o desenvolvimento de agentes antivirais, este trabalho teve como objetivo realizar uma varredura bioquímica de pequenos compostos utilizando uma forma recombinante desta enzima. Como resultado, foi possível identificar 12 inibidores de protease do vírus Zika. Esses compostos são todos produtos naturais e apresentaram forte inibição nos ensaios bioquímicos. Os valores das constantes inibitórias (Ki) para os compostos variaram de 5 nM a 8 μM. Entre os inibidores mais potentes estão alguns flavonóides como o irigenol hexa-acetato (1, Ki = 0,28 μM), katacina (2, Ki = 0,26 μM) e teaflavina galato (5, Ki = 0,40 μM). Os inibidores de outros grupos de produtos naturais incluem senosídeo A (9, Ki = 0,19 μM) e gossipol (10, Ki = 0,70 μM). Vários dos compostos obtidos são conhecidos pelos seus efeitos benéficos para a saúde humana. Portanto, eles podem constituir compostos líderes relevantes para o desenvolvimento de futuros medicamentos antivirais contra o Zika. |
publishDate |
2022 |
dc.date.issued.fl_str_mv |
2022-12-08 |
dc.date.accessioned.fl_str_mv |
2023-03-10T14:28:50Z |
dc.date.available.fl_str_mv |
2023-03-10T14:28:50Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/11600/67220 |
url |
https://repositorio.unifesp.br/11600/67220 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
76 f. |
dc.coverage.spatial.pt_BR.fl_str_mv |
São José dos Campos, SP |
dc.publisher.none.fl_str_mv |
Universidade Federal de São Paulo |
publisher.none.fl_str_mv |
Universidade Federal de São Paulo |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
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