BCX4430 inhibits the replication of rabies virus by suppressing mTOR-dependent autophagy invitro.

ABSTRACT

Rabies is a fatal neurological infectious disease caused by rabies virus (RABV). However, no effective anti-RABV drugs for treatment during the symptomatic phase are available. The novel adenosine nucleoside analog galidesivir (BCX4430) has broad-spectrum activity against a wide variety of highly pathogenic RNA viruses. In this study, we observed no apparent cytotoxicity of BCX4430 at the highest concentration of 250 µΜ, and which was displayed stronger antiviral activity against different virulent RABV in N2a or BHK-21 cells until 72 hpi. Meanwhile, BCX4430 showed greater anti-RABV activity than T-705 and anti-RABV activity similar to that of ribavirin in N2a cells. Furthermore, BCX4430 dose- and time-dependently inhibited RABV replication via mTOR-dependent autophagy inhibition in N2a cells with increased phospho-mTOR and phospho-SQSTM1 and decreased LC3-II levels. Taken together, these findings suggest that BCX4430 has potent anti-RABV activity in vitro and might provide a basis for the development of novel drug therapies against RABV.