@article{oai:muroran-it.repo.nii.ac.jp:00010422,
 author = {TSUKAMOTO, Yuta and IKEDA, Sotaro and UWAI,  Koji and 上井, 幸司 and 田口, 莉帆 and TAGUCHI, Riho and CHAYAMA, Kazuaki and SAKAGUCHI, Takemasa and NARITA, Ryo and YAO, Wan-Ling and TAKEUCHI, Fumihiko and OTAKAKI, Yukie and WATASHI, Koichi and WAKITA, Takaji and KATO, Hiroki and FUJITA, Takashi},
 issue = {5},
 journal = {PLOS ONE},
 month = {},
 note = {application/pdf, Current therapeutics for hepatitis B virus (HBV) patients such as nucleoside analogs (NAs) are effective; however, new antiviral drugs against HBV are still desired. Since the interaction between the epsilon (c) sequence of HBV pregenomic RNA and viral polymerase (Pot) is a key step in the HBV replication cycle, we aimed to identify small compounds for its inhibition, and established a pull-down assay system for the detection of c-RNA-binding-Pol. Screening showed that 5 out of 3,965 compounds inhibited c-Pol binding, and we identified rosmarinic acid, which exhibited specificity, as a potential antiviral agent. In order to examine the anti-HBV effects of rosmarinic acid, HBV-infected primary human hepatocytes from a humanized mouse liver were treated with rosmarinic acid. The rosmarinic acid treatment decreased HBV components including the amounts of extracellular HBV DNA with negligible cytotoxicity. We also investigated the combined effects of rosmarinic acid and the NA, lamivudine. rosmarinic acid slightly enhanced the anti-HBV activity of lamivudine, suggesting that the HBV replication step targeted by rosmarinic acid is distinct from that of NA. We analyzed an additional 25 rosmarinic acid derivatives, and found that 5 also inhibited c-Pol. Structural comparisons between these derivatives implied that the "two phenolic hydroxyl groups at both ends" and the "caffeic acid-like structure" of rosmarinic acid are critical for the inhibition of c-Pol binding. Collectively, our results demonstrate that rosmarinic acid inhibits HBV replication in HBV-infected cells by specifically targeting c-Pol binding.},
 title = {Rosmarinic acid is a novel inhibitor for Hepatitis B virus replication targeting viral epsilon RNA-polymerase interaction},
 volume = {13},
 year = {2018},
 yomi = {ウワイ, コウジ and タグチ, リホ}
}