Targeting host integrated stress response: lead discovery of flavonoid compounds active against coronaviruses PEDV and PDCoV

文献类型： 外文期刊

第一作者： Yi, Liang

作者： Yi, Liang;Yi, Liang;Wang, Yishuai;Zhang, Qingwen;Wang, Jiehuang;Liao, Ying;Chen, Yihan;Huang, Weixue

作者机构：

期刊名称：RSC MEDICINAL CHEMISTRY （ 影响因子：3.6； 五年影响因子：4.2 ）

ISSN：

年卷期： 2025 年 16 卷 3 期

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收录情况： SCI

摘要： Viral infections trigger the integrated stress response (ISR) in eukaryotic cells that leads to the activation of eIF2 alpha kinases, the elevation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) phosphorylation, and thereby the shutdown of global protein synthesis that viruses rely on to replicate. Coronaviruses and other viruses have evolved various subversion mechanisms to counteract the antiviral ISR. These intricate host-virus interactions may be exploited by pharmacologically activating the host ISR for the development of host-directed antivirals (HDAs), an increasingly relevant area of research. In this study, we have discovered a new class of flavonoid-based ISR activators that exhibit potent antiviral activity against porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV). PEDV and PDCoV are animal coronaviruses of great veterinary and economic importance, for which there are currently no effective therapeutics. The mechanistic study indicated that lead compounds 1-B and 1-C inhibit PEDV and PDCoV replication via upregulating eIF2 alpha phosphorylation and thereby downregulating global protein synthesis in host cells, suggesting they are HDA antivirals.

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