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Psammaplin A inhibits hepatitis C virus NS3 helicase.
MedLine Citation:
PMID:  23359228     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hepatitis C virus (HCV) is the causative agent of hepatitis C, a chronic infectious disease that can lead to development of hepatocellular carcinoma. The NS3 nucleoside triphosphatase (NTPase)/helicase has an essential role in HCV replication, and is therefore an attractive target for direct-acting antiviral strategies. In this study, we employed high-throughput screening using a photo-induced electron transfer (PET) system to identify an inhibitor of NS3 helicase from marine organism extracts. We successfully identified psammaplin A as a novel NS3 inhibitor. The dose-response relationship clearly demonstrates the inhibition of NS3 RNA helicase and ATPase activities by psammaplin A, with IC(50) values of 17 and 32 μM, respectively. Psammaplin A has no influence on the apparent K (m) value (0.4 mM) of NS3 ATPase activity, and acts as a non-competitive inhibitor. Additionally, it inhibits the binding of NS3 to single-stranded RNA in a dose-dependent manner. Furthermore, psammaplin A shows an inhibitory effect on viral replication, with EC(50) values of 6.1 and 6.3 μM in subgenomic replicon cells derived from genotypes 1b and 2a, respectively. We postulate that psammaplin A is a potential anti-viral agent through the inhibition of ATPase, RNA binding and helicase activities of NS3.
Authors:
Kazi Abdus Salam; Atsushi Furuta; Naohiro Noda; Satoshi Tsuneda; Yuji Sekiguchi; Atsuya Yamashita; Kohji Moriishi; Masamichi Nakakoshi; Masayoshi Tsubuki; Hidenori Tani; Junichi Tanaka; Nobuyoshi Akimitsu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-29
Journal Detail:
Title:  Journal of natural medicines     Volume:  -     ISSN:  1861-0293     ISO Abbreviation:  J Nat Med     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101518405     Medline TA:  J Nat Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Radioisotope Center, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
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