title: Identification of a small-molecule inhibitor of dengue virus using a replicon system.
abstract: Dengue virus (DENV) is a mosquito-borne human pathogen that causes a serious public-health threat in tropical and subtropical regions of the world. Neither a vaccine to prevent nor an effective therapeutic agent to treat DENV infection is currently available. We established a stable cell line harboring a luciferase-reporting DENV subgenomic replicon to screen for inhibitors of DENV. A total of 14,400 small-molecule (MW < 500 Da) chemicals were evaluated for their ability to reduce luciferase reporter activity in cell lysates. One effective compound was identified from the screening. This compound was found to reduce virus production but did not block virus entry in virus-based assay. Mode-of-action analysis revealed that this inhibitor suppressed viral RNA replication but did not affect replicon translation. This compound potentially could be developed as an anti-DENV agent and might be useful for dissecting the molecular mechanism of DENV replication.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, 11529, Taiwan.
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Hsu
authors.forename: Nai-Chi
authors.initials: NC
authors.lastname: Chen
authors.forename: Po-Chiang
authors.initials: PC
authors.lastname: Chen
authors.forename: Chun-Chung
authors.initials: CC
authors.lastname: Wang
authors.forename: Wei-Chieh
authors.initials: WC
authors.lastname: Cheng
authors.forename: Huey-Nan
authors.initials: HN
authors.lastname: Wu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002460:Cell Line; D003716:Dengue Virus / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D012093:Replicon / Q000187:drug effects*; D013194:Staining and Labeling; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D008156:Luciferases