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Although recent development of direct acting antiviral (DAA) compounds improved anti\u2010HCV regimens, alternative therapeutic compounds are still demanded due to an expected emergence of escape mutants for those DAAs. In order to identify novel anti\u2010HCV agents, we conducted chemical library screening for 2086 compounds using HCV Rep\u2010Feo reporter replicon in Huh7 hepatoma cells. Our screening identified retinoid derivative Tp80, which inhibits replication of HCV Rep\u2010Feo (genotype 1b) and JFH1 HCV (genotype 2a) with 0.62\u2009\u03bcM and 1.0\u2009\u03bcM, respectively, of 50% effective concentration (EC<jats:sub>50<\/jats:sub>), at which cytotoxicity is not evident for host hepatocytes. Subsequent transcriptome profiling revealed Tp80 exhibits anti\u2010HCV activity through restoration of gastrointestinal glutathione peroxidase (GI\u2010GPx), suppression of which is responsible for HCV\u2010induced oxidative stress to facilitate HCV replication. Furthermore, comparison of Tp80 with other retinoid derivatives revealed Tp80 shows best potency in both GI\u2010GPx restoration and anti\u2010HCV activity among compounds we examined. In conclusion, our current study provides Tp80 as a promising candidate of anti\u2010HCV compound, suppressing host cellular oxidative stress through a restoration of GI\u2010GPx.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.24739","type":"journal-article","created":{"date-parts":[[2016,12,6]],"date-time":"2016-12-06T10:59:16Z","timestamp":1481021956000},"page":"1224-1234","source":"Crossref","is-referenced-by-count":6,"title":["Retinoid derivative Tp80 exhibits anti\u2010hepatitis C virus activity through restoration of GI\u2010GPx expression"],"prefix":"10.1002","volume":"89","author":[{"given":"Bao Ngoc","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Anatomy and Developmental Biology Graduate School of Medicine Kyoto University Sakyo\u2010ku, Kyoto Japan"},{"name":"Biomedical Science PhD Program Tokyo Medical and Dental University Bunkyo\u2010ku, Tokyo Japan"},{"name":"Laboratory of Organic and Medicinal Chemistry Tokyo Medical and Dental University 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