Fangchinoline induces antiviral response by suppressing STING degradation

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

doi:10.1016/j.jpha.2024.100972

Volume 14 Issue 6

Jun. 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(6): 100972

Jinyong Wang, Fang Xie, Xin Jia, Xuejiao Wang, Lingdong Kong, Yiying Li, Xue Liang, Meiqi Zhang, Yuting He, Wandi Feng, Tong Luo, Yao Wang, Anlong Xu. Fangchinoline induces antiviral response by suppressing STING degradation[J]. Journal of Pharmaceutical Analysis, 2024, 14(6): 100972. doi: 10.1016/j.jpha.2024.100972

Citation:

Jinyong Wang, Fang Xie, Xin Jia, Xuejiao Wang, Lingdong Kong, Yiying Li, Xue Liang, Meiqi Zhang, Yuting He, Wandi Feng, Tong Luo, Yao Wang, Anlong Xu. Fangchinoline induces antiviral response by suppressing STING degradation[J]. Journal of Pharmaceutical Analysis, 2024, 14(6): 100972. doi: 10.1016/j.jpha.2024.100972

Citation:

Jinyong Wang, Fang Xie, Xin Jia, Xuejiao Wang, Lingdong Kong, Yiying Li, Xue Liang, Meiqi Zhang, Yuting He, Wandi Feng, Tong Luo, Yao Wang, Anlong Xu. Fangchinoline induces antiviral response by suppressing STING degradation[J]. Journal of Pharmaceutical Analysis, 2024, 14(6): 100972. doi: 10.1016/j.jpha.2024.100972

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Fangchinoline induces antiviral response by suppressing STING degradation

doi: 10.1016/j.jpha.2024.100972

a. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China;
b. School of Life Science, Beijing University of Chinese Medicine, Beijing, 100029, China;
c. 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

Funds:

This work was 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), and the Joint Fund of Beijing University of Traditional Chinese Medicine and USANA Health Sciences corporation, China (Grant No.: BUCM2023-JS-KF-032).

Received Date: Dec. 25, 2023
Accepted Date: Mar. 25, 2024
Rev Recd Date: Mar. 21, 2024
Publish Date: Mar. 28, 2024

Abstract

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.
- Fangchinoline,
- Virus,
- Type I interferons,
- Stimulator of interferon genes,
- Protein degradation

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References(45)

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