Gallic acid inhibits EMCV infection via targeting the interaction between TBK1 and IRF3 to promote IFN-β expression

ABSTRACT Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen with global distribution, which has caused huge serious economic losses to the development of the livestock industry. Gallic acid (GA) is an active ingredient of traditional Chinese medicine with wide pharmacological and biological activities and is also a potential antiviral drug. However, its antiviral effect and mechanism of anti-EMCV are still unclear. In the present study, we found that therapeutic administration of GA could significantly reduce the viral load and viral titer of EMCV to inhibit EMCV replication in a dose-dependent manner. GA could also protect cells infected by EMCV and decrease the content of capsid protein VP1 of EMCV in HEK-293 cells. Additionally, the mechanistic investigations revealed that GA might exert antiviral effects by regulating the interaction between TBK1 and IRF3 to promote the IFN-β expression. Meanwhile, GA could also alleviate EMCV-infected mice. These results indicate that GA may serve as a novel antiviral agent against EMCV infection. IMPORTANCE As a zoonotic pathogen, encephalomyocarditis virus (EMCV) causes myocarditis, encephalitis, neurological disease, reproductive disorders, and diabetes in pigs, which seriously endangers the development of the swine industry worldwide. However, due to the lack of effective commercial vaccines, there is an urgent need to develop safe and effective drugs against EMCV. Gallic acid (GA) has wide pharmacological and biological activities. However, the antiviral effect and the mechanism of GA are currently unknown. Here, we demonstrated that GA had a significant anti-EMCV effect. Further research found that GA inhibited EMCV infection via targeting the interaction between TBK1 and IRF3 to promote the IFN-β expression. These findings indicate that GA could be an effective anti-EMCV drug.