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Aim: To study the efficacy of antiviral treatment with PNA for the duck model of HBV (DHBV)-infected ducks. PNA is a 2-amine-9-(2,3-dideoxy-2,3-dihydro-β-D-arabinofuranosyl)-6-methoxy-9H-purine. Methods: The Sichuan Mallard ducklings in the hepatitis B virus model were treated with PNA, a new antiviral agent.DHBV DNA from the blood serum and liver tissues were measured at 0,5,and 10 d during the treatment and at 3 d withdrawal by real-time PCR. The duck hepatitis B surface antigen (DHBsAg) in the liver cells was observed by Immunohistochemistry (IHC). Pathological changes in the liver tissues were also observed. Control group Ⅰ was administered with distilled water and control group Ⅱ was administered with 3-thiacytidine. Treatment group Ⅰ was administered with PNA at a dose of 40 mg/kg and treatment group Ⅱ was administered perorally (po) with PNA at a dose of 80 mg/kg. Treatment group Ⅲ was administered with PNA at a dose of 20 mg/kg and treatment group Ⅳ was intravenously administered with PNA at a dose of 40 mg/kg. Each group contained 15 ducklings. Results: PNA can significantly lower the DHBV replication levels in serum and liver. Compared with control group Ⅱ, there were no significant differences in inhibiting efficacy in treatment groups Ⅰ and Ⅲ (P>0.05) and there were significant differences in inhibiting efficacy in treatment groups Ⅱ and Ⅳ (P<0.05). Interestingly, significant differences were observed at 3 d withdrawal. The DHBV replication levels in each group slightly increased at 3 d withdrawal, but rebounded slightly in the PNA treatment groups than in control group Ⅱ (P<0.05). The DHBV replication levels in the treatment groups were lower than in control group Ⅰ. The DHBV replication levels in sera had a positive relationship with that in the liver, but the DHBV replication levels in the liver was lower than that in sera. Pathological changes in the treatment groups were obviously improved and the changes were associated with liver viral DNA levels. Conclusion: The results demonstrate that PNA is a strong inhibitor of DHBV replication in the DHBV-infected duck model.