title: Determining anti-betanodavirus compounds through a GF-1 cell-based screening platform.
abstract: Betanodavirus is a highly contagious pathogen, responsible for severe losses incurred in the aquaculture industry. Currently, there are no commercially available antivirals against the virulence observed during very early stages of fish larvae development. Therefore, we developed a novel GF-1 (grouper fin cell) cell viability-based screening assay to facilitate the discovery of an anti-betanodavirus agent. The assay conditions were optimized and the robustness of the assay was confirmed by a Z' factor value ranging from 0.7 to 0.94. After screening a library of 2000 small molecule compounds, 43 compounds with a virus inhibition capacity of ⩾55% were identified. A cytochrome P450 inhibitor, proadifen hydrochloride, was validated with an EC50 value of 6.48μM and a CC50 value of 20.63μM. This compound inhibited the amplification of viral RNA by 99.68% 5days post-infection. Surprisingly, we found that 18 of 43 compounds act as neurotransmitter agents. These findings indicate a novel way of investigating the infection mechanism of betanodavirus, and suggest potential candidates for an anti-betanodavirus drug.
authors.affiliation: Institute of Fisheries Science, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Institute of Fisheries Science, College of Life Science, National Taiwan University, Taipei, Taiwan; Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan. Electronic address: yshan@ntu.edu.tw.
authors.forename: Yu-San
authors.initials: YS
authors.lastname: Han
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005399:Fishes; D030381:Nodaviridae / Q000187:drug effects*; D012367:RNA, Viral / Q000032:analysis
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral
keywords: Antiviral drug screening; Betanodavirus; Grouper culture; Nervous necrosis virus