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Antiviral Res. 2016 Sep;133:156-64. doi: 10.1016/j.antiviral.2016.08.008. Epub 2016 Aug 8.

Inhibitory effect of CDK9 inhibitor FIT-039 on hepatitis B virus propagation.

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Department of Microbiology, Graduate School of Medical Science, University of Yamanashi, Yamanashi 409-3898, Japan.
Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Division of Virology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, Kanagawa 236-0004, Japan.
Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Department of Microbiology, Graduate School of Medical Science, University of Yamanashi, Yamanashi 409-3898, Japan. Electronic address:


Current therapies for hepatitis B virus (HBV) cannot completely eliminate the HBV genome because of the stable population of covalently closed circular DNA (cccDNA) and so on. FIT-039, which is a cyclin-dependent kinase (CDK) 9 inhibitor, is known to suppress the replication of several DNA viruses including HSV, HPV and human adenovirus. In this study, we investigated the antiviral effect of FIT-039 on HBV infection. HepG2 cells expressing human sodium taurocholate cotransporting polypeptide (HepG2/NTCP cells) were infected with HBV in the presence of FIT-039. FIT-039 dose-dependently reduced intracellular viral RNA, nucleocapsid-associated viral DNA, and supernatant viral antigens without cytotoxicity in the infected cells (IC50 = 0.33 μM, CC50 > 50 μM). The antiviral activity of FIT-039 was prominent at an early phase of viral infection, although the compound did not inhibit preS1-binding to HepG2/NTCP cells. FIT-039 reduced cccDNA in HBV-replicating or HBV-infected cells. Furthermore, the antiviral activity of entecavir was significantly enhanced by the combination with FIT-039 in the chimeric mice having human hepatocytes infected with HBV. None of the mice had significant drug-related body weight or serum human-albumin concentration changes. These data suggest that CDK9 inhibitor FIT-039 is a promising antiviral candidate for HBV infection.


Antiviral; CDK9 inhibitor; HBV; Hepatitis B; Replication; cccDNA

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