Fangchinoline induces antiviral response by suppressing STING degradation  

作　　者：Jinyong Wang Fang Xie Xin Jia Xuejiao Wang Lingdong Kong Yiying Li b Xue Liang Meiqi Zhang Yuting He Wandi Feng Tong Luo Yao Wang Anlong Xu 

机构地区：[1]School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing,100029,China [2]School of Life Science,Beijing University of Chinese Medicine,Beijing,100029,China [3]Beijing Key Laboratory of Drug Target Identification and New Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100050,China

出　　处：《Journal of Pharmaceutical Analysis》2024年第6期902-913,共12页药物分析学报（英文版）

基　　金：supported by the Beijing Nova Program,China(Grant No.:20230484342);the Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(CACM),China(Grant No.:2023-QNRC2-A02);the Joint Fund of Beijing University of Traditional Chinese Medicine and USANA Health Sciences corporation,China(Grant No.:BUCM2023-JS-KF-032).

摘　　要：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.

关 键 词：FANGCHINOLINE VIRUS Type I interferons Stimulator of interferon genes Protein degradation 

分 类 号：R285[医药卫生—中药学]