The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus

摘要: Background & Aims Currently approved antivirals rarely cure hepatitis B virus (HBV) infection. Therefore additional therapeutic strategies interfering with other viral replication steps are needed. Using synthetic lipopeptides derived from the HBV envelope protein, we previously demonstrated prevention of de novo infection in vivo . We aimed at investigating ability lipopeptide Myrcludex-B to block spreading post-infection. Methods uPA/SCID mice reconstituted human hepatocytes were infected HBV. Daily subcutaneous administration was initiated either 3days, 3weeks or 8weeks post inoculation. Viral loads quantitated serum and liver, visualized by immunohistochemistry. Results efficiently prevented initially hepatocytes, as lack increase viremia, antigen levels amount HBcAg-positive determined 6weeks after treatment. blocked dissemination also when treatment started ramp-up phase infection, displaying moderate circulating virions (median 3×10 6 DNA copies/ml). Notably, treatment, not only but intrahepatic cccDNA loads, remained comparable values found sacrificed In none experimental settings, drug affected hepatocyte half-life altered virion productivity. Conclusions , hindered amplification pool hepatocytes. Administration an entry inhibitor, possibly used combination current drugs, may improve patients' outcome.