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

PeerJ. 2022 Jul 12:10:e13719. doi: 10.7717/peerj.13719. eCollection 2022.

Abstract

Background: Cyclocytidine hydrochloride (HCl) has been reported to inhibit DNA synthesis by affecting DNA polymerase. Here, we tested the antiviral effect of cyclocytidine on hepatitis B virus (HBV) DNA synthesis, which is reliant on DNA polymerase activity.

Materials and methods: Cyclocytidine HCl was treated to HBV-producing HepAD38 cells or added to an endogenous polymerase reaction, and HBV DNA was detected by Southern blot.

Results: Treatment of 20 µM 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.

Keywords: Chronic hepatitis B; Cyclocytidine hydrochloride; Hepatitis B virus; Relaxed circular DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ancitabine* / pharmacology
  • DNA, Circular* / antagonists & inhibitors
  • DNA, Circular* / drug effects
  • DNA, Circular* / genetics
  • DNA, Viral / genetics
  • DNA-Directed DNA Polymerase / genetics
  • Hepatitis B virus* / drug effects
  • Hepatitis B virus* / genetics
  • Virus Replication* / drug effects
  • Virus Replication* / genetics

Substances

  • Ancitabine
  • DNA, Circular
  • DNA, Viral
  • DNA-Directed DNA Polymerase

Grants and funding

This work was supported by the Hainan Provincial Natural Science Foundation of China (No. 820RC640), the National Natural Science Foundation of China (No. 82060365 and 81660335), the Major Science and Technology Program of Hainan Province (No. ZDKJ202003), and the Research project of Hainan academician innovation platform (No. YSPTZX202004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.