Novel Anti-Hepatitis B Virus Activity of and Its Quercetin and Kaempferol Derivatives.

Natural or plant products, because of their structural diversity, are a potential source for identifying new anti-hepatitis B virus (HBV) agents. Here, we report the anti-HBV activity of and its quercetin (QRC) and kaempferol derivatives. The anti-HBV-active methanol fraction of was subjected to chromatographic techniques, leading to isolation of three flavonols, following their structure determination by H and C NMR spectroscopies. Their cytotoxicity and anti-HBV potential were assessed using HBV reporter HepG2.2.15 cells, and their modes of action were delineated by molecular docking. The isolated compounds identified as quercetin-3--glucuronide (Q3G), quercetin-3--rhamnoside (Q3R), and kaempferol-3--glucuronide (K3G) were non-cytotoxic to HepG2.2.15 cells. The viral HBsAg/HBeAg production on day 5 was significantly inhibited by K3G (∼70.2/∼73.4%), Q3G (∼67.8/∼72.1%), and Q3R (∼63.2%/∼68.2%) as compared to QRC (∼70.3/∼74.8%) and lamivudine (∼76.5/∼84.5%) used as standards. The observed anti-HBV potential was strongly supported by analysis, which suggested their structure-based activity interfering with viral Pol/RT and core proteins. In conclusion, this is the first report on the anti-HBV activity of -derived quercitrin-3--glucuronide, quercitrin-3--rhamnoside, and kaempferol-3--glucuronide, most likely through interfering with HBV proteins.