yamashita, atsuya and Fujimoto, Yuusuke and Tamaki, Mayumi and Setiawan, Andi and Tanaka, Tomohisa and Okuyama-Dobashi, Kaori and Kasai, Hirotake and Watashi, Koichi and Wakita, Takaji and Toyama, Masaaki and Baba, Masanori and J. de Voogd, Nicole and Maekawa, Shinya and Enomoto, Nobuyuki and Tanaka, Junichi and Moriishi, Kohji Identification of Antiviral Agents Targeting Hepatitis B Virus Promoter from Extracts of Indonesian Marine Organisms by a Novel Cell-Based Screening Assay. MDPI Multidisciplinary Digital Publishing Institute.

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The current treatments of chronic hepatitis B (CHB) face a limited choice of vaccine, antibody and antiviral agents. The development of additional antiviral agents is still needed for improvement of CHB therapy. In this study, we established a screening system in order to identify compounds inhibiting the core promoter activity of hepatitis B virus (HBV). We prepared 80 extracts of marine organisms from the coral reefs of Indonesia and screened them by using this system. Eventually, two extracts showed high inhibitory activity (>95%) and low cytotoxicity (66% to 77%). Solvent fractionation, column chromatography and NMR analysis revealed that 3,5-dibromo-2-(2,4-dibromophenoxy)-phenol (compound 1) and 3,4,5-tribromo-2-(2,4-dibromophenoxy)-phenol (compound 2), which are classified as polybrominated diphenyl ethers (PBDEs), were identified as anti-HBV agents in the extracts. Compounds 1 and 2 inhibited HBV core promoter activity as well as HBV production from HepG2.2.15.7 cells in a dose-dependent manner. The EC50 values of compounds 1 and 2 were 0.23 and 0.80 µM, respectively, while selectivity indexes of compound 1 and 2 were 18.2 and 12.8, respectively. These results suggest that our cell-based HBV core promoter assay system is useful to determine anti-HBV compounds, and that two PBDE compounds are expected to be candidates of lead compounds for the development of anti-HBV drugs.

Item Type: Other
Subjects: Q Science > Q Science (General)
Depositing User: Prof Andi Setiawan
Date Deposited: 15 Feb 2022 01:11
Last Modified: 15 Feb 2022 01:11
URI: http://repository.lppm.unila.ac.id/id/eprint/39229

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