Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia

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

Publisher： MDPI

E-ISSN： 1660-3397|10|4|744-761

ISSN： 1660-3397

Source： Marine Drugs, Vol.10, Iss.4, 2012-03, pp. : 744-761

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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.