Main content area

Psammaplin A inhibits hepatitis C virus NS3 helicase

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
Natural medicines 2013 v.67 no.4 pp. 765-772
Hepatitis C virus, RNA, RNA helicases, adenosinetriphosphatase, electron transfer, genotype, hepatitis C, hepatoma, inhibitory concentration 50, nucleoside-triphosphate phosphatase, replicon, screening, virus replication
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 IC₅₀values of 17 and 32 μM, respectively. Psammaplin A has no influence on the apparent Kₘvalue (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 EC₅₀values 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.