Fangchinoline induces antiviral response by suppressing STING degradation
10.1016/j.jpha.2024.100972
- Author:
Wang JINYONG
1
;
Xie FANG
;
Jia XIN
;
Wang XUEJIAO
;
Kong LINGDONG
;
Li YIYING
;
Liang XUE
;
Zhang MEIQI
;
He YUTING
;
Feng WANDI
;
Luo TONG
;
Wang YAO
;
Xu ANLONG
Author Information
1. School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing,100029,China
- Keywords:
Fangchinoline;
Virus;
Type Ⅰ interferons;
Stimulator of interferon genes;
Protein degradation
- From:
Journal of Pharmaceutical Analysis
2024;14(6):902-913
- CountryChina
- Language:Chinese
-
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(H1 N1),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(1FN)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 degra-dation,as a promising candidate for antiviral therapy.
