Ren Sichen, Luo Yan, Tao Huimin, Wang Ping, Li Song, Yang Jingjing
Sanya Research Institute of Hainan University, Hainan University, Yazhou Bay, Sanya 572000, China.
Song Li's Academician Workstation, School of Pharmaceutical Sciences, Hainan University, Yazhou Bay, Sanya 572000, China.
Viruses. 2025 Apr 27;17(5):628. doi: 10.3390/v17050628.
Seasonal outbreaks and occasional pandemics triggered by influenza viruses annually impose considerable burdens on public health and finances. The continual evolution of viral strains with drug resistance emphasizes the urgency of discovering novel agents for influenza viruses. This study investigated a set of innovative substances derived from with antiviral potential against influenza virus strains. The top candidate, anthraquinone-2-carboxylic acid (A2CA), presented antiviral activity against diverse influenza virus strains, including those resistant to oseltamivir. In an influenza mouse model, the pre-administration of A2CA dose-dependently ameliorated influenza A virus (IAV)-mediated weight loss as well as protected mice from a lethal IAV infection. In addition, lung injury and cytokine dysregulation were mitigated. Further investigation revealed that IAV-induced activation of the RIG-I/STAT1 signaling pathway did not occur after A2CA treatment. A time-of-addition assay revealed that A2CA targeted the final phase of intracellular replication, which was further determined by molecular docking between A2CA and the IAV RdRp protein. Finally, transcriptome analysis revealed that the TP53TG3C, CFAP57 and SNX30-DT genes may be involved in the antiviral effects of A2CA. These results play a part in achieving a thorough comprehension of the capacity of A2CA to inhibit influenza virus infection.
流感病毒每年引发的季节性疫情和偶发大流行给公共卫生和财政带来了相当大的负担。病毒株耐药性的不断演变凸显了发现新型流感病毒药物的紧迫性。本研究调查了一组源自[具体来源未给出]的具有抗流感病毒株潜力的创新物质。最佳候选物蒽醌-2-羧酸（A2CA）对多种流感病毒株具有抗病毒活性，包括对奥司他韦耐药的毒株。在流感小鼠模型中，预先给予A2CA剂量依赖性地减轻了甲型流感病毒（IAV）介导的体重减轻，并保护小鼠免受致命的IAV感染。此外，减轻了肺损伤和细胞因子失调。进一步研究发现，A2CA处理后未发生IAV诱导的RIG-I/STAT1信号通路激活。添加时间实验表明，A2CA靶向细胞内复制的最后阶段，这通过A2CA与IAV RdRp蛋白之间的分子对接进一步确定。最后，转录组分析表明，TP53TG3C、CFAP57和SNX30-DT基因可能参与了A2CA的抗病毒作用。这些结果有助于全面了解A2CA抑制流感病毒感染的能力。
