High content screening of a kinase-focused library reveals compounds broadly-active against dengue viruses.
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 potent...
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Online Access: | https://doi.org/10.1371/journal.pntd.0002073 https://doaj.org/article/5f42bc3b6b364d929921faa29f151c2b |
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ftdoajarticles:oai:doaj.org/article:5f42bc3b6b364d929921faa29f151c2b 2023-05-15T15:07:10+02:00 High content screening of a kinase-focused library reveals compounds broadly-active against dengue viruses. Deu John M Cruz Andrea Cristine Koishi Juliana Bosso Taniguchi Xiaolan Li Rafaela Milan Bonotto Joo Hwan No Keum Hyun Kim Sungmin Baek Hee Young Kim Marc Peter Windisch Ana Luiza Pamplona Mosimann Luana de Borba Michel Liuzzi Michael Adsetts Edberg Hansen Claudia Nunes Duarte dos Santos Lucio Holanda Freitas-Junior 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002073 https://doaj.org/article/5f42bc3b6b364d929921faa29f151c2b EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3578765?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002073 https://doaj.org/article/5f42bc3b6b364d929921faa29f151c2b PLoS Neglected Tropical Diseases, Vol 7, Iss 2, p e2073 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002073 2022-12-31T03:38:09Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 2 e2073 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Deu John M Cruz Andrea Cristine Koishi Juliana Bosso Taniguchi Xiaolan Li Rafaela Milan Bonotto Joo Hwan No Keum Hyun Kim Sungmin Baek Hee Young Kim Marc Peter Windisch Ana Luiza Pamplona Mosimann Luana de Borba Michel Liuzzi Michael Adsetts Edberg Hansen Claudia Nunes Duarte dos Santos Lucio Holanda Freitas-Junior High content screening of a kinase-focused library reveals compounds broadly-active against dengue viruses. |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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. |
format |
Article in Journal/Newspaper |
author |
Deu John M Cruz Andrea Cristine Koishi Juliana Bosso Taniguchi Xiaolan Li Rafaela Milan Bonotto Joo Hwan No Keum Hyun Kim Sungmin Baek Hee Young Kim Marc Peter Windisch Ana Luiza Pamplona Mosimann Luana de Borba Michel Liuzzi Michael Adsetts Edberg Hansen Claudia Nunes Duarte dos Santos Lucio Holanda Freitas-Junior |
author_facet |
Deu John M Cruz Andrea Cristine Koishi Juliana Bosso Taniguchi Xiaolan Li Rafaela Milan Bonotto Joo Hwan No Keum Hyun Kim Sungmin Baek Hee Young Kim Marc Peter Windisch Ana Luiza Pamplona Mosimann Luana de Borba Michel Liuzzi Michael Adsetts Edberg Hansen Claudia Nunes Duarte dos Santos Lucio Holanda Freitas-Junior |
author_sort |
Deu John M Cruz |
title |
High content screening of a kinase-focused library reveals compounds broadly-active against dengue viruses. |
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. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002073 https://doaj.org/article/5f42bc3b6b364d929921faa29f151c2b |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 2, p e2073 (2013) |
op_relation |
http://europepmc.org/articles/PMC3578765?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002073 https://doaj.org/article/5f42bc3b6b364d929921faa29f151c2b |
op_doi |
https://doi.org/10.1371/journal.pntd.0002073 |
container_title |
PLoS Neglected Tropical Diseases |
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7 |
container_issue |
2 |
container_start_page |
e2073 |
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1766338721617018880 |