Abstract

Results: All three tested compounds reduced secreted HBV DNA levels in a concentration-dependent manner, regardless of when the treatment was started (GST-HG141 EC 50 ∼ 80 nM).The secreted HBsAg (EC 50 ∼ 1.5 microM) and HBeAg (EC 50 ∼ 1.6 microM) levels were also dose-dependently decreased by GST-HG141, but only if treatment started concurrently with infection.Similar observations were made with GLS4.ETV had no effect on HBeAg-and HBsAg levels in cell culture supernatants under neither condition.GST-HG141 potently and dose-dependently inhibited HBV cccDNA formation, but only when treatment started with the infection, and not at day 5 postinfection.No significant cytotoxicity was observed with neither compound in this study (CC 50 >10 microM).Conclusion: These data demonstrate that GST-HG141 prevents de novo synthesis of cccDNA, but has no effect on the established cccDNA pools in cultured PHH.It acts on different steps of the HBV life cycle, suggesting dual/multiple mechanisms of antiviral action.Further development of GST-HG141 for chronic HBV infections is warranted.Currently it is undergoing phase Ib-II clinical evaluations.The interim results from the ongoing phase Ib study show robust antiviral efficacy of GST-HG141 monotherapy and good safety/tolerability in chronic HBV patients.