Molecular Biology Interdepartmental Ph.D. Program, Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA, United States.
Virology. 2012 Nov 25;433(2):346-55. doi: 10.1016/j.virol.2012.08.029. Epub 2012 Sep 11.
We have previously demonstrated that quercetin, a bioflavonoid, blocks hepatitis C virus (HCV) proliferation by inhibiting NS5A-driven internal ribosomal entry site (IRES)-mediated translation of the viral genome. Here, we investigate the mechanisms of antiviral activity of quercetin and six additional bioflavonoids. We demonstrate that catechin, naringenin, and quercetin possess significant antiviral activity, with no associated cytotoxicity. Infectious virion secretion was not significantly altered by these bioflavonoids. Catechin and naringenin demonstrated stronger inhibition of infectious virion assembly compared to quercetin. Quercetin markedly blocked viral translation whereas catechin and naringenin demonstrated mild activity. Similarly quercetin completely blocked NS5A-augmented IRES-mediated translation in an IRES reporter assay, whereas catechin and naringenin had only a mild effect. Moreover, quercetin differentially inhibited HSP70 induction compared to catechin and naringenin. Thus, the antiviral activity of these bioflavonoids is mediated through different mechanisms. Therefore combination of these bioflavonoids may act synergistically against HCV.
我们之前已经证明，生物类黄酮槲皮素通过抑制 HCV 病毒 NS5A 驱动的内部核糖体进入位点（IRES）介导的病毒基因组翻译来阻断 HCV 病毒的增殖。在这里，我们研究了槲皮素和另外六种生物类黄酮的抗病毒活性机制。我们证明了儿茶素、柚皮素和槲皮素有显著的抗病毒活性，且没有伴随细胞毒性。这些生物类黄酮并没有显著改变感染性病毒粒子的分泌。与槲皮素相比，儿茶素和柚皮素对感染性病毒粒子的组装表现出更强的抑制作用。槲皮素显著阻断病毒翻译，而儿茶素和柚皮素则表现出轻微的活性。同样，槲皮素在 IRES 报告基因检测中完全阻断了 NS5A 增强的 IRES 介导的翻译，而儿茶素和柚皮素只有轻微的作用。此外，与儿茶素和柚皮素相比，槲皮素对 HSP70 的诱导有不同的抑制作用。因此，这些生物类黄酮的抗病毒活性是通过不同的机制介导的。因此，这些生物类黄酮的联合使用可能对 HCV 具有协同作用。
