Antiviral effect of chelerythrine chloride against tick-borne encephalitis virus

Tick-borne encephalitis virus (TBEV) is a neurotropic Orthoflavivirus that causes severe encephalitis and long-term neurological sequelae. Due to the limited protection from existing vaccines and the absence of effective antiviral drugs, the prevention and management of tick-borne encephalitis (TBE) remain a serious challenge. Given the homology of conserved targets and shared pathogenic mechanisms among orthoflaviviruses, we screened anti-orthoflavivirus compounds from existing research for candidates against TBEV. In this study, we identified chelerythrine chloride (CHE), a quaternary ammonium alkaloid, as the most potent compound inhibiting TBEV infection in vitro, exhibiting a 50% inhibitory concentration (IC50) of 0.85 µM and a selectivity index (SI) of 21.05. In a Kunming mouse model infected with TBEV, we found that CHE effectively increased the survival rate of mice, significantly reduced the TBEV viral load in brain tissue, and alleviated tissue inflammatory infiltration. Furthermore, mechanistic studies revealed that CHE could suppress TBEV infection via dual mechanisms: molecular docking suggests a plausible interaction with the viral E protein, which may interfere with receptor engagement, and CHE is associated with suppression of the host MAPK/ERK pathway, a mechanism that may contribute to its antiviral effect. The present study indicates that CHE has good anti-TBEV activity in vitro and in vivo, and is a potential antiviral lead compound.