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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Bibliographic Details
Published in:PLoS Neglected Tropical Diseases
Main Authors: 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
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2013
Subjects:
Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Arctic
Online Access:https://doi.org/10.1371/journal.pntd.0002073
https://doaj.org/article/5f42bc3b6b364d929921faa29f151c2b
Description
Summary: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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