Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia.
Inhibition of hepatitis C virus replication and viral helicase by ethyl acetate extract of the marine feather star Alloeocomatella polycladia.
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DOI：
10.3390/md10040744
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发表时间：
2012-04
期刊：
影响因子：
5.4
通讯作者：
Moriishi K
中科院分区：
文献类型：
--
作者：
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
丙型肝炎病毒是引起急、慢性肝炎的病原体，可导致肝硬变和肝细胞癌的发生。我们制备了61种海洋生物的提取物，并通过体外针对在丙型肝炎病毒复制中起重要作用的病毒解旋酶(NS3)的荧光试验对它们进行筛选，以确定抗丙型肝炎病毒药物的有效候选者。多枝羽星的乙酸乙酯可溶部分对NS3解旋酶活性的抑制作用最强，IC50为11.7微克/毫升。多枝黄连提取物抑制NS3与RNA的相互作用，但不抑制NS3的ATPase。此外，该提取物还能抑制来自3株1b型丙型肝炎病毒的复制子在培养细胞中的复制，其EC50值为23~44微克/毫升，与NS3解旋酶试验的IC50值相近。该提取物不诱导干扰素，也不抑制细胞生长。这些结果表明，多枝莲中的未知化合物(S)可能通过抑制丙型肝炎病毒NS3的解旋酶活性来抑制丙型肝炎病毒的复制。这项研究可能为开发治疗慢性丙型肝炎的新疗法提供一种新的途径。
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.
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DOI：
10.1038/nrd1853
发表时间：
2005-10
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Kwong AD;Rao BG;Jeang KT
通讯作者：
Jeang KT
影响因子：
5.4
作者：
FAILLA, C;TOMEI, L;DEFRANCESCO, R
通讯作者：
DEFRANCESCO, R
影响因子：
13.5
作者：
Ciesek, Sandra;von Hahn, Thomas;Steinmann, Eike
通讯作者：
Steinmann, Eike
影响因子：
3.1
作者：
Belon CA;Frick DN
通讯作者：
Frick DN
影响因子：
5.4
作者：
Gallinari, P;Brennan, D;De Francesco, R
通讯作者：
De Francesco, R