Fangchinoline induces antiviral response by suppressing STING degradation

• Main Authors: Jinyong Wang (Author), Fang Xie (Author), Xin Jia (Author), Xuejiao Wang (Author), Lingdong Kong (Author), Yiying Li (Author), Xue Liang (Author), Meiqi Zhang (Author), Yuting He (Author), Wandi Feng (Author), Tong Luo (Author), Yao Wang (Author), Anlong Xu (Author)
• Format: Book
• Published: Elsevier, 2024-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

2095-1779
10.1016/j.jpha.2024.100972