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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    • "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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    ABSTRACT: Chrysin is a derivative of flavonoid, a natural product commonly found in plants. It has been shown to afford a wide variety of pharmacological activities particularly anticancer properties. In this study, 21 chrysin derivatives with anticancer activities against human gastric adenocarcinoma (SGC-7901) and human colorectal adenocarcinoma (HT-29) cell lines were employed for quantitative structure–activity relationship (QSAR) investigation. Molecular structures were geometrically optimized at the B3LYP/6-311++g(d,p) level and their quantum chemical and molecular properties were obtained from Gaussian 09 and Dragon softwares, respectively. Significant descriptors for modeling the anticancer activities of SGC-7901 (i.e., SIC2, Mor11e, P2p, HTp, and R5e+) and HT-29 (i.e., L/Bw, BIC2, and Mor19p) cell lines were deduced from stepwise multiple linear regression (MLR) method. QSAR models were constructed using MLR and their predictivities were verified via internal (i.e., leave one-out cross-validation; LOO-CV) and external sets. The predictive performance was evaluated from their squared correlation coefficients (R 2 and Q 2) and root mean square error (RMSE). Results indicated good correlation between experimental and predicted anticancer activities as deduced from statistical parameters of internal and external sets as follows: R Tr 2 = 0.8778, RMSETr = 0.0854, Q CV 2 = 0.7315, RMSECV = 0.1375, Q Ext 2 = 0.7324, and RMSEExt = 0.1168 for QSAR models of SGC-7901 while R Tr 2 = 0.8201, RMSETr = 0.1293, Q CV 2 = 0.6829, RMSECV = 0.1735, Q Ext 2 = 0.8486, and RMSEExt = 0.1179 for QSAR models of HT-29. Furthermore, the obtained QSAR models provided pertinent insights on the structure–activity relationship of investigated compounds where molecular properties such as shape, electronegativities and polarizabilities were crucial for anticancer activity. The knowledge gained from the constructed QSAR models could serve as guidelines for the rational design of novel chrysin derivatives with potent anticancer activity.
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    • "Bioflavonoids such as quercetin, beta-carotene, resveratrol, catechins, lycopene and lutein were chosen to study the interaction with the modeled HCV helicase. These effective bioactive compounds have been reported to interfere with many disease associated biochemical processes in vitro [40]. Quercetin is reported in inhibiting initial stage of viral replication [41]. "
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