PDF(Pubmed)
Abstract：
The stimulator of interferon genes (STING), an integral adaptor protein in the DNA-sensing pathway, plays a pivotal role in the innate immune response against infections. Additionally, it presents a valuable therapeutic target for infectious diseases and cancer. We observed that fangchinoline (Fan), a bis-benzylisoquinoline alkaloid (BBA), effectively impedes the replication of vesicular stomatitis virus (VSV), encephalomyocarditis virus (EMCV), influenza A virus (H1N1), and herpes simplex virus-1 (HSV-1) in vitro. Fan treatment significantly reduced the viral load, attenuated tissue inflammation, and improved survival in a viral sepsis mouse model. Mechanistically, Fan activates the antiviral response in a STING-dependent manner, leading to increased expression of interferon (IFN) and interferon-stimulated genes (ISGs) for potent antiviral effects in vivo and in vitro. Notably, Fan interacts with STING, preventing its degradation and thereby extending the activation of IFN-based antiviral responses. Collectively, our findings highlight the potential of Fan, which elicits antiviral immunity by suppressing STING degradation, as a promising candidate for antiviral therapy.
摘要：
干扰素基因的刺激物（STING），DNA传感途径中的整合衔接蛋白，在抗感染的先天免疫反应中起着关键作用。此外,它为传染病和癌症提供了有价值的治疗靶点。我们观察到fangchinoline(Fan)，一种双苄基异喹啉生物碱（BBA），有效阻碍水疱性口炎病毒（VSV）的复制，脑心肌炎病毒（EMCV），甲型流感病毒(H1N1),和单纯疱疹病毒-1（HSV-1）的体外研究。风扇处理显著降低病毒载量，减轻组织炎症，并提高了病毒性败血症小鼠模型的存活率。机械上,风扇以STING依赖性方式激活抗病毒反应，导致干扰素（IFN）和干扰素刺激基因（ISG）的表达增加，从而在体内和体外发挥有效的抗病毒作用。值得注意的是,风扇与STING相互作用，防止其降解，从而延长基于IFN的抗病毒反应的激活。总的来说，我们的发现凸显了范的潜力，通过抑制STING降解引发抗病毒免疫，作为抗病毒治疗的有希望的候选人。
