Psammaplin A inhibits hepatitis C virus NS3 helicase

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

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    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 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.

    Original languageEnglish
    Pages (from-to)765-772
    Number of pages8
    JournalJournal of Natural Medicines
    Volume67
    Issue number4
    DOIs
    Publication statusPublished - 2013 Oct

    Fingerprint

    Viruses
    Hepacivirus
    RNA Helicases
    Adenosine Triphosphatases
    Antiviral agents
    Nucleoside-Triphosphatase
    RNA
    Aquatic Organisms
    Replicon
    Hepatitis C
    Virus Replication
    Inhibitory Concentration 50
    Antiviral Agents
    Communicable Diseases
    Hepatocellular Carcinoma
    Screening
    Chronic Disease
    Genotype
    Throughput
    psammaplin A

    Keywords

    • Hepatitis C virus
    • NS3 RNA helicase
    • Photo-induced electron transfer
    • Psammaplin A

    ASJC Scopus subject areas

    • Organic Chemistry
    • Drug Discovery
    • Pharmaceutical Science
    • Complementary and alternative medicine

    Cite this

    Salam, K. A., Furuta, A., Noda, N., Tsuneda, S., Sekiguchi, Y., Yamashita, A., ... Akimitsu, N. (2013). Psammaplin A inhibits hepatitis C virus NS3 helicase. Journal of Natural Medicines, 67(4), 765-772. https://doi.org/10.1007/s11418-013-0742-7

    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.

    In: Journal of Natural Medicines, Vol. 67, No. 4, 10.2013, p. 765-772.

    Research output: Contribution to journalArticle

    Salam, KA, Furuta, A, Noda, N, Tsuneda, S, Sekiguchi, Y, Yamashita, A, Moriishi, K, Nakakoshi, M, Tsubuki, M, Tani, H, Tanaka, J & Akimitsu, N 2013, 'Psammaplin A inhibits hepatitis C virus NS3 helicase', Journal of Natural Medicines, vol. 67, no. 4, pp. 765-772. https://doi.org/10.1007/s11418-013-0742-7
    Salam KA, Furuta A, Noda N, Tsuneda S, Sekiguchi Y, Yamashita A et al. Psammaplin A inhibits hepatitis C virus NS3 helicase. Journal of Natural Medicines. 2013 Oct;67(4):765-772. https://doi.org/10.1007/s11418-013-0742-7
    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. / Psammaplin A inhibits hepatitis C virus NS3 helicase. In: Journal of Natural Medicines. 2013 ; Vol. 67, No. 4. pp. 765-772.
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