一种非核苷酸 STING 激动剂 MSA-2 与锰协同作用增强 STING 激活，在细胞中引发强大的抗 RNA 病毒活性。
A Non-Nucleotide STING Agonist MSA-2 Synergized with Manganese in Enhancing STING Activation to Elicit Potent Anti-RNA Virus Activity in the Cells.
机构信息
Key Laboratory of Animal Medicine of Sichuan Province, College of Animal and Veterinary Sciences, Southwest Minzu University, Chengdu 610093, China.
出版信息
Viruses. 2023 Oct 24;15(11):2138. doi: 10.3390/v15112138.
Both Manganese (Mn) 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 and MSA-2 on the virus replication in the porcine cells (PK-15 cells). The results showed that both MSA-2 and Mn were able to inhibit the SVV replication in PK-15 cells. The combination of MAS-2 and Mn could confer better protection against SVV. Further studies showed that MSA-2 and Mn 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 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.
锰（Mn）和 MSA-2 均可通过干扰素基因刺激因子（STING）激活下游信号通路，并诱导 I 型干扰素的表达，这对于宿主抵抗 DNA 病毒至关重要。然而，其对 RNA 病毒的作用尚不清楚。在这项研究中，我们使用塞内卡谷病毒（SVV）作为模型 RNA 病毒来研究 Mn 和 MSA-2 对猪细胞（PK-15 细胞）中病毒复制的抑制作用。结果表明，MSA-2 和 Mn 均可抑制 PK-15 细胞中的 SVV 复制。MSA-2 和 Mn 的联合使用可以更好地保护 PK-15 细胞免受 SVV 的侵害。进一步的研究表明，MSA-2 和 Mn 可以通过 STING 激活 TBK1、IRF3 和 NFκB，并诱导 IFN-β、IL-6 和 TNF-α 的表达。本研究证实，MSA-2 与 Mn 在 STING 激活中具有协同作用，在体外产生更好的抗病毒效果，这将有助于未来开发更有效的抗病毒药物。
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