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Volume 33 Issue 6
December 2018
    Citation: Pinghu Zhang, Shuo Zhai, Jinhong Chang, Ju-Tao Guo. In Vitro Anti-hepatitis B Virus Activity of 2', 3'-Dideoxyguanosine .VIROLOGICA SINICA, 2018, 33(6) : 538-544.  http://dx.doi.org/10.1007/s12250-018-0065-7
    shu

    In Vitro Anti-hepatitis B Virus Activity of 2', 3'-Dideoxyguanosine

    cstr: 32224.14.s12250-018-0065-7
    • 1.

      Institute of Translational Medicine and Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225001, China

    • 2.

      Baruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA 18902, USA

    • 3.

      Qinghai Himalayan Experimental Animal Center, Xining 810006, China

    • Author Bio: Pinghu Zhang
    • Corresponding author: Ju-Tao Guo, ju-tao.guo@bblumberg.org, ORCID: http://orcid.org/0000-0001-5335-2788
    • Pinghu Zhang, ORCID: http://orcid.org/0000-0002-7600-4740
    • Received Date: 05 August 2018
      Accepted Date: 11 October 2018
      Published Date: 12 November 2018
      Available online: 01 December 2018
    • 2', 3'-dideoxyguanosine (DoG) has been demonstrated to inhibit duck hepatitis B virus (DHBV) replication in vivo in a duck model of HBV infection. In the current study, the in vitro antiviral effects of DoG on human and animal hepadnaviruses were investigated. Our results showed that DoG effectively inhibited HBV, DHBV, and woodchuck hepatitis virus (WHV) replication in hepatocyte-derived cells in a dose-dependent manner, with 50% effective concentrations (EC50) of 0.3 ± 0.05, 6.82 ± 0.25, and 23.0 ± 1.5 njmol/L, respectively. Similar to other hepadnaviral DNA polymerase inhibitors, DoG did not alter the levels of intracellular viral RNA but induced the accumulation of a less-than-full-length viral RNA species, which was recently demonstrated to be generated by RNase H cleavage of pgRNA. Furthermore, using a transient transfection assay, DoG showed similar antiviral activity against HBV wild-type, 3TC-resistant rtA181V, and adefovirresistant rtN236T mutants. Our results suggest that DoG has potential as a nucleoside analogue drug with anti-HBV activity.
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      In Vitro Anti-hepatitis B Virus Activity of 2', 3'-Dideoxyguanosine

        Corresponding author: Ju-Tao Guo, ju-tao.guo@bblumberg.org
      • Pinghu Zhang, ORCID: http://orcid.org/0000-0002-7600-4740
      • 1. Institute of Translational Medicine and Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225001, China
      • 2. Baruch S. Blumberg Institute, Hepatitis B Foundation, Doylestown, PA 18902, USA
      • 3. Qinghai Himalayan Experimental Animal Center, Xining 810006, China
      • Received Date: 05 August 2018
      • Accepted Date: 11 October 2018
      • Published Date: 12 November 2018

      Abstract: 2', 3'-dideoxyguanosine (DoG) has been demonstrated to inhibit duck hepatitis B virus (DHBV) replication in vivo in a duck model of HBV infection. In the current study, the in vitro antiviral effects of DoG on human and animal hepadnaviruses were investigated. Our results showed that DoG effectively inhibited HBV, DHBV, and woodchuck hepatitis virus (WHV) replication in hepatocyte-derived cells in a dose-dependent manner, with 50% effective concentrations (EC50) of 0.3 ± 0.05, 6.82 ± 0.25, and 23.0 ± 1.5 njmol/L, respectively. Similar to other hepadnaviral DNA polymerase inhibitors, DoG did not alter the levels of intracellular viral RNA but induced the accumulation of a less-than-full-length viral RNA species, which was recently demonstrated to be generated by RNase H cleavage of pgRNA. Furthermore, using a transient transfection assay, DoG showed similar antiviral activity against HBV wild-type, 3TC-resistant rtA181V, and adefovirresistant rtN236T mutants. Our results suggest that DoG has potential as a nucleoside analogue drug with anti-HBV activity.

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