Abstract
Combination therapy with ribavirin, interferon, and viral protease inhibitors could be expected to elicit a high level of sustained virologic response in patients infected with hepatitis C virus (HCV). However, several severe side effects of this combination therapy have been encountered in clinical trials. In order to develop more effective and safer anti-HCV compounds, we employed the replicon systems derived from several strains of HCV to screen 84 extracts from 54 organisms that were gathered from the sea surrounding Okinawa Prefecture, Japan. The ethyl acetate-soluble extract that was prepared from marine sponge Amphimedon sp. showed the highest inhibitory effect on viral replication, with EC50 values of 1.5 and 24.9 µg/ml in sub-genomic replicon cell lines derived from genotypes 1b and 2a, respectively. But the extract had no effect on interferon-inducing signaling or cytotoxicity. Treatment with the extract inhibited virus production by 30% relative to the control in the JFH1-Huh7 cell culture system. The in vitro enzymological assays revealed that treatment with the extract suppressed both helicase and protease activities of NS3 with IC50 values of 18.9 and 10.9 µg/ml, respectively. Treatment with the extract of Amphimedon sp. inhibited RNA-binding ability but not ATPase activity. These results suggest that the novel compound(s) included in Amphimedon sp. can target the protease and helicase activities of HCV NS3.
Highlights
Hepatitis C virus (HCV) is an enveloped RNA virus of the genusHepacivirus of the Flaviviridae family
Several natural products have been reported as anti-viral agents against hepatitis C virus (HCV) replication
Epigallocatechin 3-gallate, and proanthocyanidins, which were prepared from milk thistle, green tea, and blueberry leaves, respectively, have exhibited inhibitory activity against HCV replication in cultured cells [34,35,36,37]
Summary
Hepatitis C virus (HCV) is an enveloped RNA virus of the genusHepacivirus of the Flaviviridae family. Hepatitis C virus (HCV) is an enveloped RNA virus of the genus. More than 170 million patients persistently infected with HCV have been reported worldwide, leading to liver diseases including steatosis, cirrhosis, and hepatocellular carcinoma [1,2]. The genome of HCV is characterized as a single positive-strand RNA with a nucleotide length of. 9.6 kb, flanked by 59 and 39-untranslated regions (UTRs). The genomic RNA encodes a large polyprotein consisting of approximately 3,000 amino acids [3], which is translated under the control of an internal ribosome entry site (IRES) located within the. 59-UTR of the genomic RNA [4]. The translated polyprotein is cleaved by host and viral proteases, resulting in 10 mature viral. Extract C-29EA inhibited the production of infectious viral particles, viral RNA, and core protein from
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
