Diallyl trisulfide inhibits in vitro replication of the Japanese encephalitis virus by modulating autophagy via mTOR-dependent pathway.

Japanese encephalitis is a neurological disease caused by the mosquito-borne Japanese encephalitis virus (JEV). The clinically approved antiviral drugs for JEV infection are not available. In our present study, we investigated the antiviral activity of garlic oil and its key organosulfur compounds against JEV. The garlic oil showed anti-JEV activity in Neuro-2a cells at a 20 μg/ml concentration. Further, the components of garlic oil, i.e., diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), were screened for their anti-JEV activity. DATS was active among these compounds and displayed higher antiviral activity against JEV than DAS and DADS. Moreover, DATS inhibited JEV replication in a dose- and time-dependent manner. Mechanistic investigations revealed the activation of mTOR signaling associated protein levels (phospho-mTOR, mTOR, phospho-AKT, AKT) and phospho-p62 autophagy marker in JEV-infected Neuro-2a cells after 48 h post-treatment with DATS. These results demonstrate that DATS inhibits JEV replication by suppressing autophagy via mTOR-dependent pathway.