Phorbol Myristate Acetate Inhibits Senecavirus A Replication by Activating IKBKE-Mediated IFN Pathway and NF-κB Signal

Senecavirus A (SVA) is an emerging picornavirus causing vesicular disease indistinguishable from foot-and-mouth disease virus (FMDV). So far, there are no commercial vaccines and effective therapeutic drugs against SVA Infection in China. Here, a library of 112 compounds were screened, and we found that phorbol myristate acetate plays an antagonistic role in the early stage of SVA Infection. And phorbol 12-myristate 13-acetate (PMA) upregulates the expression of IKBKE, and activates IFN pathway and NF-κB signal. However, the PMA-mediated detrimental effect on SVA is reversed in IKBKE-deficient cells or when the NF-κB pathway blocked by BAY-117082, implying that IKBKE is the target for the Antiviral effect of PMA. Additionally, PMA possesses Antiviral effect on multiple RNA viruses, including porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), and encephalomyocarditis virus (EMCV). Overall, our findings offer that PMA inhibits SVA replication by activating IKBKE-mediated IFN pathway and NF-κB signal. And it might be a promising candidate for further broad-spectrum therapeutic development.