Divergent antiviral effects of bioflavonoids on the hepatitis C virus life cycle. Virology

Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA, United States. Electronic address: .
Virology (Impact Factor: 3.32). 09/2012; 433(2):346-55. DOI: 10.1016/j.virol.2012.08.029
Source: PubMed


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.

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Available from: Santanu Raychaudhuri
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    • "Flavonoids, a naturally occurring polyphenolic compound found in plants, are essential components of natural products that had been found to exert a wide variety of pharmacological activities such as Electronic supplementary material The online version of this article (doi:10.1007/s00044-014-1260-1) contains supplementary material, which is available to authorized users. antioxidant (Heim et al., 2002; Pietta, 2000), antimicrobial (Cushnie and Lamb, 2005; Takahashi et al., 2004), antiinflammatory (Rathee et al., 2009; Serafini et al., 2010), anticancer (Batra and Sharma, 2013; Kandaswami et al., 2005), and antiviral (Ibrahim et al., 2013; Khachatoorian et al., 2012) activities. In fact, there are in excess of 4,000 types of biologically active flavonoid derivatives identified to date that include flavonol, flavanone, isoflavone, flavones , anthocyanin, and catechins sub-classes (Nijveldt et al., 2001). "
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