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

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2025-03-10 DOI:10.1016/j.antiviral.2025.106141

Ruikun Du , Jiawen Sun , Chunlei Zhang , Chenglong Chen , Zinuo Chen , Varada Anirudhan , Qinghua Cui , Hualin Wang , Lijun Rong , Yun-Jia Ning

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引用次数: 0

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.

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坎普奈德作为一种新型广谱抗病毒药物增强I型干扰素信号

广谱抗病毒药物（bsa）具有独特的优势，可以有效地对抗广泛的现有和不可预测的新发病毒感染。宿主I型干扰素（IFN）应答作为一种普遍的非特异性防御多种病毒感染，为开发新的bsa提供了有吸引力的靶点。在本研究中，我们发现山奈啡黄酮是I型IFN激活Janus激酶/信号转导和转录激活因子（JAK/STAT）信号通路的增强剂，促进IFN刺激基因（ISGs）的表达和细胞抗病毒状态的建立。此外，我们的研究清楚地表明，山奈哌啶通过与内源性或外源性ifn协同作用，对多种病毒（包括高致病性重症发热伴血小板减少综合征病毒（SFTSV）和克里米亚-刚果出血热病毒（CCHFV））具有强效的BSA活性。机制研究进一步揭示，山奈普胺通过阻断细胞因子信号抑制因子3介导的负反馈，延长I型IFN刺激JAK/STAT信号的持续时间。综上所述，我们认为坎普奈德是一种有潜力的新型BSA药物，值得进一步开发。

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来源期刊

Antiviral research 医学-病毒学

CiteScore

17.10

自引率

3.90%

发文量

157

审稿时长

34 days

期刊介绍： Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.