Pholiota squarrosa lectin (PhoSL), a lectin binding to core-fucose specifically, inhibits HBV infection

Glycosylation in host cells and viruses is an important factor in viral infection and a target for anti-viral therapy. Hepatitis B virus (HBV) is a major pathogen causing acute /chronic hepatitis. To achieve the cure, new anti-HBV agents are needed. Here we found that Pholiota squarrosa lectin (PhoSL), a lectin that specifically binds core-fucose, inhibited HBV infection to a human NTCP-expressing HepG2 cell called C4, a cell line susceptible to HBV infection. PhoSL bound to HBV particles. Fut8KO-C4 cells markedly lost HBV infectivity, and addition of PhoSL facilitated the loss of infectivity. Furthermore, we found that PhoSL blocked the activation of epidermal growth factor receptor (EGFR), a process enhancing HBV infection. Observation of the dynamics of fluorescent labeled PhoSL on C4 cells on the infection HBV showed that PhoSL-bound HBV was incorporated into host cells, suggesting that PhoSL could inhibit HBV infection after internalization. Since PhoSL reduced cccDNA formation, the process from internalization to cccDNA formation should be impaired by PhoSL. We believe that this finding should lead to development of new anti-HBV agents.