%0 Journal Article
%T Fangchinoline induces antiviral response by suppressing STING degradation.
%A Wang J
%A Xie F
%A Jia X
%A Wang X
%A Kong L
%A Li Y
%A Liang X
%A Zhang M
%A He Y
%A Feng W
%A Luo T
%A Wang Y
%A Xu A
%J J Pharm Anal
%V 14
%N 6
%D 2024 Jun
%M 39027910
%F 14.026
%R 10.1016/j.jpha.2024.100972
%X 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.