干扰素基因刺激剂 (STING) 是 DNA 传感途径中的一个整合接头蛋白，在针对感染的先天免疫反应中发挥着关键作用。此外，它还为传染病和癌症提供了有价值的治疗靶点。我们观察到防己啉 (Fan) 是一种双苄基异喹啉生物碱 (BBA)，可有效阻止水泡性口炎病毒 (VSV)、脑心肌炎病毒 (EMCV)、甲型流感病毒 (H1N1) 和单纯疱疹病毒 1 (HSV) 的复制-1) 体外。风扇治疗显着降低了病毒载量，减轻了组织炎症，并提高了病毒性脓毒症小鼠模型的存活率。从机制上讲，Fan 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，Fan 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，我们的研究结果凸显了 Fan 作为一种有前途的抗病毒治疗候选者的潜力，它通过抑制 STING 降解来引发抗病毒免疫。© 2024 由 Elsevier B.V. 代表西安交通大学出版。

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.© 2024 Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.