Document Detail


Inhibition of both protease and helicase activities of hepatitis C virus NS3 by an ethyl acetate extract of marine sponge Amphimedon sp.
MedLine Citation:
PMID:  23144928     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Yuusuke Fujimoto; Kazi Abdus Salam; Atsushi Furuta; Yasuyoshi Matsuda; Osamu Fujita; Hidenori Tani; Masanori Ikeda; Nobuyuki Kato; Naoya Sakamoto; Shinya Maekawa; Nobuyuki Enomoto; Nicole J de Voogd; Masamichi Nakakoshi; Masayoshi Tsubuki; Yuji Sekiguchi; Satoshi Tsuneda; Nobuyoshi Akimitsu; Naohiro Noda; Atsuya Yamashita; Junichi Tanaka; Kohji Moriishi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-07
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-11-12     Completed Date:  2013-05-09     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e48685     Citation Subset:  IM    
Affiliation:
Department of Microbiology, Division of Medicine, Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acetates
Animals
Antiviral Agents / isolation & purification,  pharmacology*
Cell Line
Complex Mixtures / chemistry
Hepacivirus / drug effects*,  enzymology,  genetics
Interferon-alpha / metabolism
Porifera / chemistry*
Protease Inhibitors / isolation & purification,  pharmacology*
Signal Transduction / drug effects
Viral Nonstructural Proteins / antagonists & inhibitors*
Virus Replication / drug effects
Chemical
Reg. No./Substance:
0/Acetates; 0/Antiviral Agents; 0/Complex Mixtures; 0/Interferon-alpha; 0/NS3 protein, hepatitis C virus; 0/Protease Inhibitors; 0/Viral Nonstructural Proteins; 76845O8NMZ/ethyl acetate
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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