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

  • Viruses. 2023 Oct 24;15(11):2138. doi: 10.3390/v15112138.
Hanrui Lin  1 ,  Rui Zhang  1 ,  Hanyi Xiang  1 ,  Xinqian Lin  1 ,  Xiongting Huang  1 ,  Jingsong Chen  1 ,  Long Zhou  1 ,  Zhidong Zhang  1 ,  Yanmin Li  1
Affiliations
  • 1. Key Laboratory of Animal Medicine of Sichuan Province, College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu 610093, China.
PMID: 38005816 DOI: 10.3390/v15112138
Abstract

Both Manganese (Mn2+) 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 Mn2+ and MSA-2 on the virus replication in the porcine cells (PK-15 cells). The results showed that both MSA-2 and Mn2+ were able to inhibit the SVV replication in PK-15 cells. The combination of MAS-2 and Mn2+ could confer better protection against SVV. Further studies showed that MSA-2 and Mn2+ 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 Mn2+ 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.

Keywords
MSA-2; Seneca Valley virus; antiviral effect; manganese; stimulator of interferon genes.
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