title: Identification of three antiviral inhibitors against Japanese encephalitis virus from library of pharmacologically active compounds 1280.
abstract: Japanese encephalitis virus (JEV) can cause severe central nervous disease with a high mortality rate. There is no antiviral drug available for JEV-specific treatment. In this study, a cytopathic-effect-based, high-throughput screening assay was developed and applied to screen JEV inhibitors from Library of Pharmacologically Active Compounds 1280. The antiviral effects of three hit compounds including FGIN-1-27, cilnidipine, and niclosamide were evaluated in cells by western blotting, indirect immunofluorescence assay, and plaque reduction assay. A time-of-addition assay proved that all three compounds inhibited JEV at the stage of replication. The EC50s of FGIN-1-27, cilnidipine, and niclosamide were 3.21, 6.52, and 5.80 µM, respectively, while the selectivity indexes were 38.79, 30.67, and 7.49. FGIN-1-27 and cilnidipine have high efficiency and selectivity against JEV. This study provided two JEV antiviral inhibitors as candidates for treatment of JEV infection.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Jin'e
authors.initials: J
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Leqiang
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Guiqing
authors.initials: G
authors.lastname: Peng
authors.affiliation: College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Shengbo
authors.initials: S
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Song
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D015153:Blotting, Western; D004095:Dihydropyridines / Q000494:pharmacology; D004664:Encephalitis Virus, Japanese / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D007210:Indoleacetic Acids / Q000494:pharmacology; D009534:Niclosamide / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D004095:Dihydropyridines; D007210:Indoleacetic Acids; C081306:N,N-di-n-hexyl-2-(4-fluorophenyl)indole-3-acetamide; D009534:Niclosamide; C065927:cilnidipine