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香叶木素抗甲型H1N1流感病毒研究

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目的 筛选香叶木素与甲型H1N1相关蛋白的结合位点,评价香叶木素抗甲型H1N1病毒的效果,分析抗病毒作用效果和机制,筛选备选的抗病毒单体药物。方法 应用分子对接软件Discovery Studio预测香叶木素分子与甲型H1N1病毒相关蛋白的结合位点,筛选可能结合的蛋白位点,并利用等离子共振法对香叶木素分子与初步筛选的甲型H1N1病毒的相关蛋白进行体外分子对接实验,进一步明确香叶木素分子的抗H1N1作用靶点。利用ELISA法以及xCELLigence RTCA DP实时细胞分析技术检测香叶木素对病毒的抑制作用。结合两部分检测结果综合评价香叶木素对甲型H1N1病毒的抗病毒药效,明确作用机制。结果 香叶木素与甲型H1N1病毒的HA、NP、NA蛋白均有一定程度的结合,且在无毒计量下对H1N1病毒HA蛋白具有靶向性。香叶木素对甲型H1N1病毒的体外抑制率高达91。97%,其抑制效果在24 h内相对稳定。结论 香叶木素通过靶向甲型H1N1流感病毒,可发挥高效的抗甲型H1N1流感病毒活性,为香叶木素等传统中药单体成分在抗甲型流感的药物开发上提供了新的思路。
The anti-H1N1 influenza virus activity of diosmetin
Objective To screen the theoretical binding sites of diosmetin and functional proteins of H1N1 influ-enza virus,so as to evaluate the antiviral effect of diosmetin on H1N1 and analyze the mechanism behind it,and to screen candidate of anti-H1N1 drug monomers.Methods Discovery Studio molecular docking was used to pre-dict and screen the binding sites of diosmetin to the functional proteins of H1N1.Surface Plasmon Resonance(SPR)analysis were used to identify the diosmetin combination possibility to the screened H1N1 functional pro-teins and further identify the anti-H1N1 target of diosmetin.The inhibitory effect of diosmetin on H1N1 influenza virus was detected by ELISA and xCELLigence RTCA DP cell analysis technique.The anti-H1N1 efficacy was e-valuated comprehensively by combining the above analysis results.Results Diosmetin has the ability of binding to HA,NP and NA proteins of H1N1 influenza virus with certain affinities,and was capable of targeting HA protein under non-toxic concentration.The in vitro inhibition rate of diosmetin to H1N1 reached 91.97%,and inhibitory effect was relatively stable within 24 hours.Conclusion By targeting H1N1 virus on certain target,diosmetin can exhibit highly effective anti-H1N1 activity.Our study provides a new research orientations for the application of anti-influenza of diosmetin and other ingredients of traditional Chinese medicine.

H1N1 virusdiosmetinmolecular dockingantiviral effect

郝峻、王明连、赵洪武、郝彦哲、李劲涛

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北京工业大学化学与生命科学学院环境与病毒肿瘤学北京市重点实验室,抗病毒药物北京市国际科技合作基地,北京 100124

传染病溯源预警与智能决策全国重点实验室,中国疾病预防控制中心病毒病预防控制所,北京 100052

H1N1病毒 香叶木素 分子对接 抗病毒特性

北京市自然科学基金北京市教委科技一般项目国家重点研发计划

M22032KM2019100050042021YFC2301103

2024

遵义医科大学学报
遵义医科大学

遵义医科大学学报

CSTPCD
ISSN:2096-8159
年,卷(期):2024.47(5)