2. Academic Validation
  3. Kaempferide enhances type I interferon signaling as a novel broad-spectrum antiviral agent

Kaempferide enhances type I interferon signaling as a novel broad-spectrum antiviral agent

  • Antiviral Res. 2025 Mar 10:237:106141. doi: 10.1016/j.antiviral.2025.106141.
Ruikun Du 1,  Jiawen Sun 2,  Chunlei Zhang 3,  Chenglong Chen 4,  Zinuo Chen 5,  Varada Anirudhan 6,  Qinghua Cui 7,  Hualin Wang 8,  Lijun Rong 9,  Yun-Jia Ning 10
Affiliations

Affiliations

  • 1 Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, 266041, China. Electronic address: ruikun@sdutcm.edu.cn.
  • 2 State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071/430207, China; University of Chinese Academy of Sciences, Beijing, 101408, China.
  • 3 Department of Emergency, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
  • 4 College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, China.
  • 5 Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, China.
  • 6 Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, 60612, USA.
  • 7 Qingdao Academy of Chinese Medical Sciences, Shandong University of Traditional Chinese Medicine, Qingdao, 266041, China.
  • 8 State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071/430207, China; State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071/430207, China.
  • 9 Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, 60612, USA. Electronic address: lijun@uic.edu.
  • 10 State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071/430207, China; State Key Laboratory of Virology and Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071/430207, China; Hubei Jiangxia Laboratory, Wuhan, 430207, China. Electronic address: nyj@wh.iov.cn.
PMID: 40074087 DOI: 10.1016/j.antiviral.2025.106141
Abstract

Broad-spectrum antivirals (BSAs) possess unique advantages of being effective against a wide range of both existing and unpredictable emerging viral infections. The host type I interferon (IFN) response serves as a universal defense against diverse viral infections nonspecifically, providing attractive targets to develop novel BSAs. In this study, we identified the flavonoid kaempferide as an enhancer of the type I IFN activated Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, promoting the expression of IFN stimulated genes (ISGs) and the establishment of cellular Antiviral status. Additionally, our study clearly demonstrated that kaempferide exhibits potent BSA activity against diverse viruses including the highly pathogenic severe fever with thrombocytopenia syndrome virus (SFTSV) and Crimean-Congo hemorrhagic fever virus (CCHFV), by synergizing with either endogenous or exogenous IFNs. Mechanistic study further revealed that kaempferide acts by preventing the suppressor of cytokine signaling 3-mediated negative feedback, prolonging the duration of type I IFN stimulated JAK/STAT signaling. In summary, we herein report kaempferide as a novel potential BSA agent that deserves further development in the future.

Keywords

Broad-spectrum antiviral; Immune-modulator; Kaempferide; Type I interferon.

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