1. Fangchinoline induces antiviral response by suppressing STING degradation
- Author
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Jinyong Wang, Fang Xie, Xin Jia, Xuejiao Wang, Lingdong Kong, Yiying Li, Xue Liang, Meiqi Zhang, Yuting He, Wandi Feng, Tong Luo, Yao Wang, and Anlong Xu
- Subjects
Fangchinoline ,Virus ,Type I interferons ,Stimulator of interferon genes ,Protein degradation ,Therapeutics. Pharmacology ,RM1-950 - 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.
- Published
- 2024
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