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  • Title: A preliminary investigation on the mechanism of action of 4-(8-(2-ethylimidazole)octyloxy)-arctigenin against IHNV.
    Author: Shan L, Wang H, Hu Y.
    Journal: Virus Res; 2021 Mar; 294():198287. PubMed ID: 33418024.
    Abstract:
    Arctigenin derivatives form an elite class of naturally occurring compounds that possess promising antiviral therapeutic perspectives. In a previous study, we design and synthesize a arctigenin derivative, 4-(8-(2-ethylimidazole)octyloxy)-arctigenin (EOA), to evaluate its antiviral activity on infectious hematopoietic necrosis virus (IHNV). In this study, we find that the half maximal inhibitory concentrations (IC50) of EOA on IHNV nucleoprotein (N), phosphoprotein (P), matrix protein (M), nonvirion protein (NV) and polymerase (L) mRNA expression is 0.92, 0.80, 0.98, 0.89 and 0.87 μM, respectively. Mechanistically, our results show that EOA do not damage the viral particles directly, indicating EOA does not possess antiviral activity by destroying virions. Viral binding assays reveal that EOA do not interfere with IHNV adsorption. Because rapamycin has been shown to exhibit anti-IHNV activity by inducing autophagy of epithelioma papulosum cyprini (EPC) cells, we further investigate the relationship between EOA and autophagy in EPC cells. Autophagy fluorescence detection shows that EPC cells have a strong autophagy body after being treated with derivative EOA. The electron microscopy results show that EOA could induce typical autophagosomes which are representative structures of autophagy activation. Moreover, the punctate accumulation of green fluorescence-tagged microtubule-associate protein 1 light chain 3 (LC3) and the protein conversion from LC3-I to LC3-II are respectively confirmed by confocal fluorescence microscopy and western blotting. Overall, these findings demonstrate that EOA plays an anti-IHNV role via inducing autophagy in EPC cells.
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