Antiviral Activity of Isoimperatorin Against Influenza A Virus in vitro and its Inhibition of Neuraminidase.
Antiviral Activity of Isoimperatorin Against Influenza A Virus in vitro and its Inhibition of Neuraminidase.
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DOI：
10.3389/fphar.2021.657826
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发表时间：
2021
影响因子：
5.6
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Lai Y;Han T;Zhan S;Jiang Y;Liu X;Li G
甲型流感病毒（Influenza A virus，IAV）严重威胁人类健康，是全球性的重大公共卫生问题。随着全球抗流感病毒药物耐药性的显著增加，迫切需要开发新的抗病毒药物，特别是来自天然产物的药物。异欧前胡素是一种具有活性的天然呋喃香豆素类化合物，具有抗凝血、镇痛、抗炎、抗菌、抗肿瘤等多种药理活性，受到越来越多的关注。本研究探讨了异欧前胡素在体外对甲型流感病毒的抗病毒作用及其机制。异欧前胡素显示出广谱抗病毒作用，特别是针对A/FM/1/47（H1N1）、A/WSN/33（H1N1，S31 N，金刚烷胺抗性）、A/波多黎各/8/34（H1N1）和A/鸡/广东/1996（H9 N2）病毒株。不同给药方式的实验结果表明，异欧前胡素在治疗方式下具有最佳的抗病毒活性。进一步的加药时间实验结果表明，在病毒复制周期的后期（6- 8h、8-10 h）加入异欧前胡素，表现出有效的抗病毒作用，病毒产量分别降低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表明，异欧前胡素对NA介导的子代病毒释放发挥抑制作用。分子对接实验模拟了异欧前胡素与NA蛋白氨基酸残基的直接相互作用。总之，异欧前胡素可用作预防和治疗甲型流感病毒的潜在药物。
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 in vitro 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.
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影响因子：
5.6
作者：
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通讯作者：
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DOI：
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发表时间：
2013-10-02
期刊：
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影响因子：
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通讯作者：
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影响因子：
2.7
作者：
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通讯作者：
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影响因子：
5.1
作者：
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通讯作者：
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DOI：
10.1038/nrd2175
发表时间：
2006-12
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
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通讯作者：
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