Lai Yanni, Han Tiantian, Zhan Shaofeng, Jiang Yong, Liu Xiaohong, Li Geng
Guangzhou University of Chinese Medicine, Guangzhou, China.
The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Front Pharmacol. 2021 Apr 13;12:657826. doi: 10.3389/fphar.2021.657826. eCollection 2021.
Influenza A virus (IAV) poses a severe threat to human health and is a major public health problem worldwide. As global anti-influenza virus drug resistance has increased significantly, there is an urgent need to develop new antiviral drugs, especially drugs from natural products. Isoimperatorin, an active natural furanocoumarin, exhibits a broad range of pharmacologic activities including anticoagulant, analgesic, anti-inflammatory, antibacterial, anti-tumor, and other pharmacological effects, so it has attracted more and more attention. In this study, the antiviral and mechanistic effects of isoimperatorin on influenza A virus were studied. Isoimperatorin illustrated a broad-spectrum antiviral effect, especially against the A/FM/1/47 (H1N1), A/WSN/33 (H1N1, S31N, amantadine resistant), A/Puerto Rico/8/34 (H1N1), and A/Chicken/Guangdong/1996 (H9N2) virus strains. The experimental results of different administration modes showed that isoimperatorin had the best antiviral activity under the treatment mode. Further time-of-addition experiment results indicated that when isoimperatorin was added at the later stage of the virus replication cycle (6-8 h, 8-10 h), it exhibited an effective antiviral effect, and the virus yield was reduced by 81.4 and 84.6%, respectively. In addition, isoimperatorin had no effect on the expression of the three viral RNAs (mRNA, vRNA, and cRNA). Both the neuraminidase (NA) inhibition assay and CETSA demonstrated that isoimperatorin exerts an inhibitory effect on NA-mediated progeny virus release. The molecular docking experiment simulated the direct interaction between isoimperatorin and NA protein amino acid residues. In summary, isoimperatorin can be used as a potential agent for the prevention and treatment of influenza A virus.
甲型流感病毒（IAV）对人类健康构成严重威胁，是全球主要的公共卫生问题。随着全球抗流感病毒耐药性显著增加，迫切需要开发新的抗病毒药物，尤其是来自天然产物的药物。异欧前胡素是一种活性天然呋喃香豆素，具有广泛的药理活性，包括抗凝、镇痛、抗炎、抗菌、抗肿瘤等药理作用，因此受到越来越多的关注。本研究对异欧前胡素抗甲型流感病毒的作用及其机制进行了研究。异欧前胡素表现出广谱抗病毒作用，尤其对A/FM/1/47（H1N1）、A/WSN/33（H1N1，S31N，耐金刚烷胺）、A/波多黎各/8/34（H1N1）和A/鸡/广东/1996（H9N2）病毒株有效。不同给药方式的实验结果表明，异欧前胡素在该治疗方式下具有最佳的抗病毒活性。进一步的加样时间实验结果表明，当在病毒复制周期后期（6 - 8小时、8 - 10小时）加入异欧前胡素时，它表现出有效的抗病毒作用，病毒产量分别降低了81.4%和84.6%。此外，异欧前胡素对三种病毒RNA（mRNA、vRNA和cRNA）的表达没有影响。神经氨酸酶（NA）抑制试验和CETSA均表明，异欧前胡素对NA介导的子代病毒释放具有抑制作用。分子对接实验模拟了异欧前胡素与NA蛋白氨基酸残基之间的直接相互作用。综上所述，异欧前胡素可作为预防和治疗甲型流感病毒的潜在药物。
