In Vitro Anti-hepatitis B Virus Activity of 2′,3′-Dideoxyguanosine
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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 μmol/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 adefovir-resistant rtN236T mutants. Our results suggest that DoG has potential as a nucleoside analogue drug with anti-HBV activity.
KeywordsHBV Woodchuck hepatitis virus (WHV) Hepatitis B Antiviral Nucleoside analogues
The work was supported in part by the Program for New Century Excellent Talents in University (Program No. NCET-12-0975); by the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry; and by Jiangsu Overseas research & training program for University Prominent Young and Middle-aged Teachers and Presidents (for Pinghu Zhang); Qinghai Province High-end Innovative Talent Thousand Talents Program (for Pinghu Zhang).
PZ mainly contributed to the design, acquisition, analysis, and interpretation of data for this work; ZS contributed to the sequencing of viral RNA species; JC and JTG contributed to the experimental design and data interpretation of this work.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Animal and Human Rights Statement
The authors declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.
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