High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pntd.0002073 http://hdl.handle.net/11449/74531 |
Resumo: | Dengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates. © 2013 Cruz et al. |
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High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Virusesalpha2a interferonchloroquinephosphotransferase inhibitorribavirinaffinity chromatographyanimal cellantiviral activityChikungunya alphaviruscomputer modelcomputer programcontrolled studyDengue virusdose responsedrug structuregenotypehigh throughput screeninghumanhuman cellnonhumannucleotide sequencepeptide libraryvalidation processviral disease immunofluorescence assayAntiviral AgentsCell LineDengue VirusDrug DiscoveryHepatocytesHigh-Throughput Screening AssaysHumansMicrobial Sensitivity TestsDengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates. © 2013 Cruz et al.Center for Neglected Diseases Drug Discovery (CND3) Institut Pasteur Korea, Seongnam-si, Gyeonggi-doInstituto Carlos Chagas Fundação Oswaldo Cruz Paraná (ICC/FIOCRUZ-PR), Curitiba, ParanáUniversidade Federal do Paraná (UFPR), Curitiba, ParanáUniversidade Estadual Paulista Júlio de Mesquita Filho, Araraquara, São PauloImage Mining Group (IMG) Institut Pasteur Korea, Seongnam-si, Gyeonggi-doUniversidade Feevale, Novo Hamburgo, Rio Grande do SulApplied Molecular Virology (AMV) Institut Pasteur Korea, Seongnam-si, Gyeonggi-doEarly Discovery Program Institut Pasteur Korea, Seongnam-si, Gyeonggi-doUniversidade Estadual Paulista Júlio de Mesquita Filho, Araraquara, São PauloInstitut Pasteur KoreaFundação Oswaldo Cruz Paraná (ICC/FIOCRUZ-PR)Universidade Federal do Paraná (UFPR)Universidade Estadual Paulista (Unesp)Universidade FeevaleCruz, Deu John M.Koishi, Andrea CristineTaniguchi, Juliana Bosso [UNESP]Li, XiaolanMilan Bonotto, RafaelaNo, Joo HwanKim, Keum HyunBaek, SungminKim, Hee YoungWindisch, Marc PeterPamplona Mosimann, Ana Luizade Borba, LuanaLiuzzi, MichelHansen, Michael Adsetts EdbergNunes Duarte dos Santos, ClaudiaFreitas-Junior, Lucio Holanda2014-05-27T11:28:20Z2014-05-27T11:28:20Z2013-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1371/journal.pntd.0002073PLoS Neglected Tropical Diseases, v. 7, n. 2, 2013.1935-27271935-2735http://hdl.handle.net/11449/7453110.1371/journal.pntd.0002073WOS:0003156449000372-s2.0-848747819072-s2.0-84874781907.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLoS Neglected Tropical Diseases4.3672,5892,589info:eu-repo/semantics/openAccess2024-01-22T06:23:46Zoai:repositorio.unesp.br:11449/74531Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T23:40:38.571117Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses |
title |
High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses |
spellingShingle |
High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses Cruz, Deu John M. alpha2a interferon chloroquine phosphotransferase inhibitor ribavirin affinity chromatography animal cell antiviral activity Chikungunya alphavirus computer model computer program controlled study Dengue virus dose response drug structure genotype high throughput screening human human cell nonhuman nucleotide sequence peptide library validation process viral disease immunofluorescence assay Antiviral Agents Cell Line Dengue Virus Drug Discovery Hepatocytes High-Throughput Screening Assays Humans Microbial Sensitivity Tests |
title_short |
High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses |
title_full |
High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses |
title_fullStr |
High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses |
title_full_unstemmed |
High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses |
title_sort |
High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses |
author |
Cruz, Deu John M. |
author_facet |
Cruz, Deu John M. Koishi, Andrea Cristine Taniguchi, Juliana Bosso [UNESP] Li, Xiaolan Milan Bonotto, Rafaela No, Joo Hwan Kim, Keum Hyun Baek, Sungmin Kim, Hee Young Windisch, Marc Peter Pamplona Mosimann, Ana Luiza de Borba, Luana Liuzzi, Michel Hansen, Michael Adsetts Edberg Nunes Duarte dos Santos, Claudia Freitas-Junior, Lucio Holanda |
author_role |
author |
author2 |
Koishi, Andrea Cristine Taniguchi, Juliana Bosso [UNESP] Li, Xiaolan Milan Bonotto, Rafaela No, Joo Hwan Kim, Keum Hyun Baek, Sungmin Kim, Hee Young Windisch, Marc Peter Pamplona Mosimann, Ana Luiza de Borba, Luana Liuzzi, Michel Hansen, Michael Adsetts Edberg Nunes Duarte dos Santos, Claudia Freitas-Junior, Lucio Holanda |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Institut Pasteur Korea Fundação Oswaldo Cruz Paraná (ICC/FIOCRUZ-PR) Universidade Federal do Paraná (UFPR) Universidade Estadual Paulista (Unesp) Universidade Feevale |
dc.contributor.author.fl_str_mv |
Cruz, Deu John M. Koishi, Andrea Cristine Taniguchi, Juliana Bosso [UNESP] Li, Xiaolan Milan Bonotto, Rafaela No, Joo Hwan Kim, Keum Hyun Baek, Sungmin Kim, Hee Young Windisch, Marc Peter Pamplona Mosimann, Ana Luiza de Borba, Luana Liuzzi, Michel Hansen, Michael Adsetts Edberg Nunes Duarte dos Santos, Claudia Freitas-Junior, Lucio Holanda |
dc.subject.por.fl_str_mv |
alpha2a interferon chloroquine phosphotransferase inhibitor ribavirin affinity chromatography animal cell antiviral activity Chikungunya alphavirus computer model computer program controlled study Dengue virus dose response drug structure genotype high throughput screening human human cell nonhuman nucleotide sequence peptide library validation process viral disease immunofluorescence assay Antiviral Agents Cell Line Dengue Virus Drug Discovery Hepatocytes High-Throughput Screening Assays Humans Microbial Sensitivity Tests |
topic |
alpha2a interferon chloroquine phosphotransferase inhibitor ribavirin affinity chromatography animal cell antiviral activity Chikungunya alphavirus computer model computer program controlled study Dengue virus dose response drug structure genotype high throughput screening human human cell nonhuman nucleotide sequence peptide library validation process viral disease immunofluorescence assay Antiviral Agents Cell Line Dengue Virus Drug Discovery Hepatocytes High-Throughput Screening Assays Humans Microbial Sensitivity Tests |
description |
Dengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates. © 2013 Cruz et al. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-02-01 2014-05-27T11:28:20Z 2014-05-27T11:28:20Z |
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://dx.doi.org/10.1371/journal.pntd.0002073 PLoS Neglected Tropical Diseases, v. 7, n. 2, 2013. 1935-2727 1935-2735 http://hdl.handle.net/11449/74531 10.1371/journal.pntd.0002073 WOS:000315644900037 2-s2.0-84874781907 2-s2.0-84874781907.pdf |
url |
http://dx.doi.org/10.1371/journal.pntd.0002073 http://hdl.handle.net/11449/74531 |
identifier_str_mv |
PLoS Neglected Tropical Diseases, v. 7, n. 2, 2013. 1935-2727 1935-2735 10.1371/journal.pntd.0002073 WOS:000315644900037 2-s2.0-84874781907 2-s2.0-84874781907.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS Neglected Tropical Diseases 4.367 2,589 2,589 |
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.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808129541898502144 |