Cyclocytidine hydrochloride inhibits the synthesis of relaxed circular DNA of hepatitis B virus

Background. Cydocytidine hydrochloride (HCl) has been reported to inhibit DNA synthesis by affecting DNA polymerase. Here, we tested the antiviral effect of cydocytidine on hepatitis B virus (HBV) DNA synthesis, which is reliant on DNA polymerase activity. Materials and Methods. Cydocytidine HCl was treated to HBV-producing HepAD38 rPlls or added to an endogenous polymerase reaction, and HBV DNA was detected by Southern blot. Results. Treatment of 20 mu M cyclocytidine HCl significantly decreased the production of relaxed circular (rc) DNA in HepAD38 cells and block rcDNA synthesis in endogenous polymerase reaction (EPR), a cell free assay, possibly by inhibiting the HBV DNA polymerase activity. Conclusion. Cyclocytidine HCl could inhibit the synthesis of HBV rcDNA, the precursor of covalently closed circular DNA, and this result provides a case for the usage of "old" drugs for "new" applications.