Potential for Core Fucose-Targeted Therapy Against HBV Infection of Human Normal Hepatocytes

Core fucose is one of the most important glycans in HBV infection. In this study, we investigated whether PhoSL, a lectin that specifically binds to core fucose, exerts an inhibitory effect in an HBV infection model of normal human hepatocytes. Similar to previous studies using hepatocellular carcinoma cells (HepG2-C4), coexistence of PhoSL during HBV infection inhibited HBe antigen production and HBV cccDNA in normal human hepatocytes in a PhoSL concentration-dependent manner. Furthermore, this effect of PhoSL was found to be able to suppress HBe antigen production in a treatment period-dependent manner even when PhoSL was administered after HBV infection. The mechanisms of HBV infection inhibition by PhoSL that have been elucidated so far are physical inhibition by binding to the HBV receptor and inhibition of HBV entry into cells by inhibiting phosphorylation of EGFR, a co-receptor for NTCP. Furthermore, this study suggested that PhoSL may also inhibit HBV proliferation in cells through some mechanism. PhoSL is a lectin derived from edible mushrooms that is resistant to acid and heat. In addition, it has a low molecular weight and can be chemically synthesized, so it is expected to be used clinically as a new carbohydrate therapy for HBV in the future.