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https://www.arca.fiocruz.br/handle/icict/15677
HIGH CONTENT SCREENING OF A KINASE-FOCUSED LIBRARY REVEALS COMPOUNDS BROADLY-ACTIVE AGAINST DENGUE VIRUSES
Author
Cruz, Deu John M.
Koishi, Andrea Cristine
Taniguchi, Juliana Bosso
Xiaolan, L
Bonotto, Rafaela Milan
No, Joo Hwan
Kim, Keum Hyun
Baek, Sungmin
Kim, Hee Young
Windisch, Marc Peter
Mosimann, Ana Luiza Pamplona
Borba, Luana de
Liuzzi, Michel
Hansen, Michael Adsetts Edberg
Santos, Claudia Nunes Duarte dos
Freitas-Junior, Lucio Holanda
Koishi, Andrea Cristine
Taniguchi, Juliana Bosso
Xiaolan, L
Bonotto, Rafaela Milan
No, Joo Hwan
Kim, Keum Hyun
Baek, Sungmin
Kim, Hee Young
Windisch, Marc Peter
Mosimann, Ana Luiza Pamplona
Borba, Luana de
Liuzzi, Michel
Hansen, Michael Adsetts Edberg
Santos, Claudia Nunes Duarte dos
Freitas-Junior, Lucio Holanda
Affilliation
Institut Pasteur Korea. Center for Neglected Diseases Drug Discovery. Seongnam-si, South Korea.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. / Universidade Federal do Paraná. Curitiba, PR, Brasil.
Universidade Estadual Paulista. Araraquara, SP, Brasil.
Institut Pasteur Korea. Image Mining Group.Seongnam-si, South Korea.
Universidade Feevale. Novo Hamburgo, RS, Brasil.
Institut Pasteur Korea. Center for Neglected Diseases Drug Discovery. Seongnam-si, South Korea.
Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea.
Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea.
Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea.
Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Institut Pasteur Korea. Early Discovery Program. Seongnam-si, South Korea.
Institut Pasteur Korea. Image Mining Group. Seongnam-si, South Korea.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Institut Pasteur Korea. Center for Neglected Diseases Drug Discovery. Seongnam-si, South Korea.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil. / Universidade Federal do Paraná. Curitiba, PR, Brasil.
Universidade Estadual Paulista. Araraquara, SP, Brasil.
Institut Pasteur Korea. Image Mining Group.Seongnam-si, South Korea.
Universidade Feevale. Novo Hamburgo, RS, Brasil.
Institut Pasteur Korea. Center for Neglected Diseases Drug Discovery. Seongnam-si, South Korea.
Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea.
Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea.
Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea.
Institut Pasteur Korea. Applied Molecular Virology. Seongnam-si, South Korea.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Institut Pasteur Korea. Early Discovery Program. Seongnam-si, South Korea.
Institut Pasteur Korea. Image Mining Group. Seongnam-si, South Korea.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Institut Pasteur Korea. Center for Neglected Diseases Drug Discovery. Seongnam-si, South Korea.
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.
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