Xiao Chai Hu Tang inhibits CVB1 virus infection of CCFS-1 cells through the induction of Type I interferon expression

Coxsackie B virus type 1 (CVB1) infection is known to cause high morbidity and mortality in children, however, there is no effective drug for treating this disease. The present study aimed to examine the antiviral activity of Xiao Chai Hu Tang (XCHT), a popular herbal drug for treating viral and bacterial infections, against CVB1 infection and its mechanisms of action. Our data showed that XCHT neutralized the CVB1-induced cytopathic effect in human neonatal foreskin fibroblast cell line (CCFS-1/KMC), with IC50 (virus-induced cytopathic effect by 50%) and EC50 (concentration of 50% effectiveness) values around 12.39 and 50.93 μg/ml, respectively. Its CC50 (concentration of 50% cellular cytotoxicity) and SI (selective index) values were 945.75 μg/ml and 18.92, respectively. These results suggest that XCHT possessed anti-CVB1 activity, and showed no effect on CCFS-1 cell viability and growth at concentration 250 μg/ml. The time-of-addition studies showed that XCHT (50, 100 and 200 μg/ml) added at various time of preinfection (− 1 to − 3 h), coinfection (0 h) and postinfection (1∼3 h) could inhibit CVB1 infection. Interestingly, XCHT also showed an inhibition on viral replication through the induction of IFN-α/β expression. In conclusion, XCHT possessed antiviral activity against CVB1 infection. It interfered the early stage of viral replication (prophylactic effect) and viral replication after infection (therapeutic effect) through the induction of Type I interferon expression.