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.
Mar Drugs. 2012 Apr;10(4):744-761. doi: 10.3390/md10040744. Epub 2012 Mar 28.
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.
丙型肝炎病毒 (HCV) 是急性和慢性肝炎的致病因子，可导致肝纤维化和肝细胞癌的发展。我们从 61 种海洋生物中制备提取物，并通过针对病毒解旋酶（NS3）的体外荧光测定法对其进行筛选，以鉴定抗 HCV 药物的有效候选物。多枝海盘车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 µg/mL。A. polycladia 的提取物抑制 NS3 与 RNA 之间的相互作用，但不抑制 NS3 的 ATP 酶活性。此外，该提取物可抑制来自三种基因型 1b 的 HCV 株的复制子在培养细胞中的复制，EC50 值为 23 至 44 µg/mL，与 NS3 解旋酶测定的 IC50 值相似。该提取物不诱导干扰素或抑制细胞生长。这些结果表明，A. polycladia 中包含的未知化合物可以通过抑制 HCV NS3 的解旋酶活性来抑制 HCV 复制。本研究可能为慢性丙型肝炎的新型治疗方法提供了新的途径。
