The development of new agents to target HBV cccDNA is urgently needed because of the limitations of current available drugs for treatment of hepatitis B. By using a cell-based assay in which the production of HBeAg is in a cccDNA-dependent manner, we screened a compound library derived from Chinese herbal remedies for inhibitors against HBV cccDNA. Three hydrolyzable tannins, specifically punicalagin, punicalin and geraniin, emerged as novel anti-HBV agents. These compounds significantly reduced the production of secreted HBeAg and cccDNA in a dose-dependent manner in our assay, without dramatic alteration of viral DNA replication. Furthermore, punicalagin did not affect precore/core promoter activity, pgRNA transcription, core protein expression, or HBsAg secretion. By employing the cell-based cccDNA accumulation and stability assay, we found that these tannins significantly inhibited the establishment of cccDNA and modestly facilitated the degradation of preexisting cccDNA. Collectively, our results suggest that hydrolyzable tannins inhibit HBV cccDNA production via a dual mechanism through preventing the formation of cccDNA and promoting cccDNA decay, although the latter effect is rather minor. These hydrolyzable tannins may serve as lead compounds for the development of new agents to cure HBV infection.

In HepG2.117 cells, EGCG inhibits HBV replication by impairing HBV replicative intermediates of DNA synthesis and such inhibition results in reduced production of HBV covalently closed circular DNA.

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The shrinking and drying up of wetlands in arid and semiarid areas of China have been widely observed in the recent years, but there has been no consensus on whether the aggravation is caused by human activities or by global climate warming. For a better understanding of the cause, this study investigates the dynamic changes of Baiyangdian Lake wetland over the last 40 years. It is shown that since the 1980s, Baiyangdian Lake has suffered from an insufficient water input and shrunk considerably. By using SPSS11.0, this study undertakes a detailed analysis on the significance of the effects of the possible driving factors for the degradation. It is identified that the North China Plain has been warming up significantly in recent years, which causes a significant reduction in the precipitation and inflow to the lake. Although human disturbances such as the irrigation and storage of water in reservoirs do not play a decisive role, they accelerate the degradation and their effects should be minimized.