A Non-Nucleotide STING Agonist MSA-2 Synergized with Manganese in Enhancing STING Activation to Elicit Potent Anti-RNA Virus Activity in the Cells

Both Manganese (Mn(2+)) and MSA-2 can activate the downstream signal pathway through stimulator of interferon genes (STING) and induce the expression of type I interferon, which is important for hosts to protect against DNA viruses. However, its effect on RNA viruses remains unknown. In this study, we used Seneca Valley virus (SVV) as a model RNA virus to investigate the inhibitory effects of Mn(2+) and MSA-2 on the virus replication in the porcine cells (PK-15 cells). The results showed that both MSA-2 and Mn(2+) were able to inhibit the SVV replication in PK-15 cells. The combination of MAS-2 and Mn(2+) could confer better protection against SVV. Further studies showed that MSA-2 and Mn(2+) could activate TBK1, IRF3 and NFκB through STING and induce the expression of IFN-β, IL-6 and TNF-α. The present study confirmed that MSA-2 synergized with Mn(2+) in STING activation to generate a better antiviral effect in vitro, which would be helpful for the further development of effective antiviral drugs in the future.