Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia.
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 IC(50) 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 EC(50) value of 23 to 44 µg/mL, which is similar to the IC(50) 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.
Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan.
Atsuya
A
Yamashita
Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Kazi Abdus
KA
Salam
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.
Atsushi
A
Furuta
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.
Yasuyoshi
Y
Matsuda
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.
Osamu
O
Fujita
Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Hidenori
H
Tani
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.
Yoshihisa
Y
Fujita
Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan.
Yuusuke
Y
Fujimoto
Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Masanori
M
Ikeda
Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Nobuyuki
N
Kato
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Naoya
N
Sakamoto
First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan.
Shinya
S
Maekawa
First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan.
Nobuyuki
N
Enomoto
Institute of Medical Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
Masamichi
M
Nakakoshi
Institute of Medical Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
Masayoshi
M
Tsubuki
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Yuji
Y
Sekiguchi
Department of Life Science and Medical Bio-Science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Satoshi
0000-0002-4624-5359
S
Tsuneda
Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Nobuyoshi
N
Akimitsu
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan.
Naohiro
N
Noda
Department of Chemistry, Biology and Marine Science, University of the Ryukyus, Nishihara, Okinawa 903-0213, Japan.
Junichi
J
Tanaka
Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo-shi, Yamanashi 409-3898, Japan.
Kohji
0000-0002-9542-5188
K
Moriishi
D000085:Acetates / Q000737:chemistry; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D059001:Aquatic Organisms / Q000737:chemistry*; D004261:DNA Replication / Q000187:drug effects; D004447:Echinodermata / Q000737:chemistry*; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D007372:Interferons / Q000378:metabolism; D020365:RNA Helicases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012367:RNA, Viral / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D000085:Acetates; D000998:Antiviral Agents; D012367:RNA, Viral; C007650:ethyl acetate; D007372:Interferons; D000251:Adenosine Triphosphatases; D020365:RNA Helicases