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Plos Neglected Tropical Diseases : High Content Screening of a Kinase-focused Library Reveals Compounds Broadly-active Against Dengue Viruses, Volume 7

By Michael, Scott F.


Description
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 kinasefocused 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 liverderived 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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