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

Marine Drugs

Atsuya Yamashita⁸  Kazi Abdus Salam²  Atsushi Furuta⁴  Yasuyoshi Matsuda⁴  Osamu Fujita⁴  Hidenori Tani²  Yoshihisa Fujita³  Yuusuke Fujimoto⁸  Masanori Ikeda⁵  Nobuyuki Kato⁵  Naoya Sakamoto⁹  Shinya Maekawa⁶  Nobuyuki Enomoto⁶  Masamichi Nakakoshi¹  Masayoshi Tsubuki¹  Yuji Sekiguchi⁴  Satoshi Tsuneda⁷  Nobuyoshi Akimitsu²  Naohiro Noda⁴  Junichi Tanaka¹ 

[1] Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan;University Education Center, University of the Ryukyus, Okinawa, 1 Senbaru, Nishihara, Okinawa 903-0213, Japan;Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, 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;First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan;Department of Life Science and Medical Bio-Science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan;;Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, JapanDepartment of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan;

关键词: marine organism;    Alloeocomatella polycladia;    hepatitis C virus;    NS3 helicase;   

DOI  :  10.3390/md10040744

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.