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 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. © 2013 cruz et al.