Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia

Atsuya Yamashita, Kazi Abdus Salam, Atsushi Furuta, Yasuyoshi Matsuda, Osamu Fujita, Hidenori Tani, Yoshihisa Fujita, Yuusuke Fujimoto, Masanori Ikeda, Nobuyuki Kato, Naoya Sakamoto, Shinya Maekawa, Nobuyuki Enomoto, Masamichi Nakakoshi, Masayoshi Tsubuki, Yuji Sekiguchi, Satoshi Tsuneda, Nobuyoshi Akimitsu, Naohiro Noda, Junichi TanakaKohji Moriishi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC50 of 11.7 μg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC50 value of 23 to 44 μg/mL, which is similar to the IC50 value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C.

Original languageEnglish
Pages (from-to)744-761
Number of pages18
JournalMarine Drugs
Volume10
Issue number4
DOIs
Publication statusPublished - 2012 Apr

Keywords

  • Alloeocomatella polycladia
  • Hepatitis C virus
  • Marine organism
  • NS3 helicase

ASJC Scopus subject areas

  • Drug Discovery

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    Yamashita, A., Salam, K. A., Furuta, A., Matsuda, Y., Fujita, O., Tani, H., Fujita, Y., Fujimoto, Y., Ikeda, M., Kato, N., Sakamoto, N., Maekawa, S., Enomoto, N., Nakakoshi, M., Tsubuki, M., Sekiguchi, Y., Tsuneda, S., Akimitsu, N., Noda, N., ... Moriishi, K. (2012). Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia. Marine Drugs, 10(4), 744-761. https://doi.org/10.3390/md10040744