Primary identification of compounds targeting hepatitis B virus capsid formation from the FDA approved drugs

Objective To identify the candidates targeting capsid formation of HBV by screening a FDA approved drug library. Methods SRluc-HBc6 cells, which indicates the formation of HBc dimers by the split luciferase complementation (SLC), were used as the 1st round screening model. Compounds identified by the 1st round screening were tested for their ability to inhibit the formation of capsid by using particle gel assay. Southern blotting was employed to detect the anti-HBV activity of these compounds on the replication of HBV DNA. Results According to the Rluc activities of SRluc-HBc6 cells, 5 candidates were screened out of 1 434 drugs in the first round screening. They are chlorambucil, cladribine, methylene blue, sorafenib, and regorafenib. Further tests showed that chlorambucil inhibited the replication of HBV DNA in HepAD38 cells by reducing the formation of HBV core dimers and capsids. Conclusion Chlorambucil inhibit HBV DNA replication in vitro by reducing HBV core dimers and the formation of capsid.