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 <i>Pholiota squarrosa</i> lectin (PhoSL), a lectin that specifically binds to core fucose, exerts an inhibitory effect in an HBV infection model of normal human hepatocytes. Similarly to previous studies using hepatocellular carcinoma cells (HepG2-C4), the 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. Our previous research has revealed that the mechanism by which PhoSL inhibits HBV infection is through physical inhibition by binding to the HBV receptor and inhibition of HBV entry into cells by inhibiting the phosphorylation of EGFR, a co-receptor for NTCP. Furthermore, this study suggested that PhoSL may also inhibit HBV proliferation in cells through other mechanisms that require further investigation. PhoSL is a lectin, derived from edible <i>Pholiota squarrosa</i> (shaggy scalycap) 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.