Department of Pharmacy, Guangdong Second Provincial General Hospital, No.466 Middle Xingang Road, Guangzhou, 510317, China.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, No. 1838 Shatai South Road, Baiyun District, Guangzhou, 510515, China.
Microbes Infect. 2023 Mar-Apr;25(3):105062. doi: 10.1016/j.micinf.2022.105062. Epub 2022 Oct 22.
With the prevalence of novel strains and drug-resistant influenza viruses, there is an urgent need to develop effective and low-toxicity anti-influenza therapeutics. Regulation of the type I interferon antiviral response is considered an attractive therapeutic strategy for viral infection. Pterostilbene, a 3,5-dimethoxy analog of resveratrol, is known for its remarkable pharmacological activity. Here, we found that pterostilbene effectively inhibited influenza A virus infection and mainly affected the late stages of viral replication. A mechanistic study showed that the antiviral activity of pterostilbene might promote the induction of antiviral type I interferon and expression of its downstream interferon-stimulated genes during viral infection. The same effect of pterostilbene was also observed in the condition of polyinosinic-polycytidylic acid (poly I:C) transfection. Further study showed that pterostilbene interacted with influenza non-structural 1 (NS1) protein, inhibited ubiquitination mediated degradation of RIG-I and activated the downstream antiviral pathway, orchestrating an antiviral state against influenza virus in the cell. Taken together, pterostilbene could be a promising anti-influenza agent for future antiviral drug exploitation and compounds with similar structures may provide new options for the development of novel inhibitors against influenza A virus (IAV).
随着新型流感病毒株和耐药性流感病毒的流行，迫切需要开发有效且低毒的抗流感治疗药物。调节 I 型干扰素抗病毒反应被认为是一种有吸引力的病毒感染治疗策略。紫檀芪是白藜芦醇的 3,5-二甲氧基类似物，以其显著的药理活性而闻名。在这里，我们发现紫檀芪能有效抑制甲型流感病毒感染，主要影响病毒复制的晚期阶段。一项机制研究表明，紫檀芪的抗病毒活性可能在病毒感染过程中促进诱导抗病毒 I 型干扰素及其下游干扰素刺激基因的表达。紫檀芪在多聚肌苷酸-多聚胞苷酸（poly I:C）转染的情况下也有相同的作用。进一步的研究表明，紫檀芪与流感非结构蛋白 1（NS1）蛋白相互作用，抑制 RIG-I 介导的泛素化降解，并激活下游抗病毒途径，在细胞中对抗流感病毒产生抗病毒状态。总之，紫檀芪可能是一种有前途的抗流感药物，可用于未来的抗病毒药物开发，具有类似结构的化合物可能为开发新型抗甲型流感病毒（IAV）抑制剂提供新的选择。
