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Psammaplin A inhibits hepatitis C virus NS3 helicase.

Authors
  • Salam, Kazi Abdus
  • Furuta, Atsushi
  • Noda, Naohiro
  • Tsuneda, Satoshi
  • Sekiguchi, Yuji
  • Yamashita, Atsuya
  • Moriishi, Kohji
  • Nakakoshi, Masamichi
  • Tsubuki, Masayoshi
  • Tani, Hidenori
  • Tanaka, Junichi
  • Akimitsu, Nobuyoshi
Type
Published Article
Journal
Journal of natural medicines
Publication Date
Oct 01, 2013
Volume
67
Issue
4
Pages
765–772
Identifiers
DOI: 10.1007/s11418-013-0742-7
PMID: 23359228
Source
Medline
License
Unknown

Abstract

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 IC₅₀ values of 17 and 32 μM, respectively. Psammaplin A has no influence on the apparent Km 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 EC₅₀ 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.

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