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Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia
Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan
Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan
Department of Life Science and Medical Bio-Science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan
University Education Center, University of the Ryukyus, Okinawa, 1 Senbaru, Nishihara, Okinawa 903-0213, Japan
Marine Learning Center, 2-95-101 Miyagi, Chatan, Okinawa 901-0113, Japan
Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan
First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan
Institute of Medical Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan
Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 9 February 2012; in revised form: 17 March 2012 / Accepted: 19 March 2012 / Published: 28 March 2012
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.
Keywords: marine organism; Alloeocomatella polycladia; hepatitis C virus; NS3 helicase
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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.; Tanaka, J.; Moriishi, K. Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia. Mar. Drugs 2012, 10, 744-761.
Yamashita A, Salam KA, 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, Tanaka J, Moriishi K. Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia. Marine Drugs. 2012; 10(4):744-761.
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. 2012. "Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia." Mar. Drugs 10, no. 4: 744-761.