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- Title
High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses.
- Authors
Cruz, Deu John M.; Koishi, Andrea Cristine; Taniguchi, Juliana Bosso; Xiaolan Li; Bonotto, Rafaela Milan; Joo Hwan No; Keum Hyun Kim; Sungmin Baek; Hee Young Kim; Windisch, Marc Peter; Mosimann, Ana Luiza Pamplona; de Borba, Luana; Liuzzi, Michel; Hansen, Michael Adsetts Edberg; Santos, Claudia Nunes Duarte dos; Freitas-Junior, Lucio Holanda
- 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.
- Subjects
DENGUE; DENGUE viruses; FLAVIVIRUSES; VIRUS diseases; CELL lines; INFECTION
- Publication
PLoS Neglected Tropical Diseases, 2013, Vol 7, Issue 2, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0002073