MA026, an anti-hepatitis C virus compound, opens tight junctions of the epithelial cell membrane

MA026 is an antiviral natural compound against hepatitis C virus (HCV). It was recently reported that MA026 binds claudin-1 (CLDN1) and inhibits HCV infection. Although CLDN1 is an important component of tight junctions (TJ) in the epithelial cell layer, the effects of MA026 on the TJ barrier function remained to be revealed. Here we report that MA026 irreversibly opens the TJ. MA026 irreversibly increased FD4 permeability and decreased transepithelial electrical resistance (TER) for at least 5 h. Although MA026 increased Ca²⁺ influx in layered MDCKII cells, the Ca²⁺ influx was less than that of capsaicin, a reversible TJ opener. Moreover, MA026 did not induce the dephosphorylation of cofilin and reorganization of F-actin structure. Although the mechanism is left to be disclosed, these results suggest that MA026 is a novel irreversible TJ opener probably by targeting CLDN1.