Author | Cruz, Deu John M. | |
Author | Koishi, Andrea Cristine | |
Author | Taniguchi, Juliana Bosso | |
Author | Xiaolan, L | |
Author | Bonotto, Rafaela Milan | |
Author | No, Joo Hwan | |
Author | Kim, Keum Hyun | |
Author | Baek, Sungmin | |
Author | Kim, Hee Young | |
Author | Windisch, Marc Peter | |
Author | Mosimann, Ana Luiza Pamplona | |
Author | Borba, Luana de | |
Author | Liuzzi, Michel | |
Author | Hansen, Michael Adsetts Edberg | |
Author | Santos, Claudia Nunes Duarte dos | |
Author | Freitas-Junior, Lucio Holanda | |
Access date | 2016-09-05T17:06:37Z | |
Available date | 2016-09-05T17:06:37Z | |
Document date | 2013 | |
Citation | CRUZ, Deu John M. et al. High content screening of a kinase-focused library reveals compounds broadly-active against dengue viruses. PLOS Neglected Tropical Diseases, v. 7, n. 2, p. 1-13, 2013. | pt_BR |
ISSN | 1935-2727 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/15677 | |
Sponsorship | This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2012-00011). | pt_BR |
Language | por | pt_BR |
Rights | open access | pt_BR |
Title | High content screening of a kinase-focused library reveals compounds broadly-active against Dengue viruses | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.pntd.0002073 | pt_BR |
Abstract | 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. | pt_BR |
Affilliation | Institut Pasteur Korea. Center for Neglected Diseases Drug Discovery. Seongnam-si, South Korea. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. / Universidade Federal do Paraná. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Universidade Estadual Paulista. Araraquara, SP, Brasil. | pt_BR |
Affilliation | Institut Pasteur Korea. Image Mining Group.Seongnam-si, South Korea. | pt_BR |
Affilliation | Universidade Feevale. Novo Hamburgo, RS, Brasil. | pt_BR |
Affilliation | Institut Pasteur Korea. Center for Neglected Diseases Drug Discovery. Seongnam-si, South Korea. | pt_BR |
Affilliation | Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea. | pt_BR |
Affilliation | Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea. | pt_BR |
Affilliation | Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea. | pt_BR |
Affilliation | Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Institut Pasteur Korea. Early Discovery Program. Seongnam-si, South Korea. | pt_BR |
Affilliation | Institut Pasteur Korea. Image Mining Group. Seongnam-si, South Korea. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. | pt_BR |
Affilliation | Institut Pasteur Korea. Center for Neglected Diseases Drug Discovery. Seongnam-si, South Korea. | pt_BR |
Subject | Dengue | pt_BR |
Subject | Flavivirus | pt_BR |
Subject | Antiviral Agents | En |
Subject | Arboviruses | En |
DeCS | Arbovirus | pt_BR |
DeCS | Antivirais | pt_BR |