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Probing the effect of quercetin 3-glucoside from Dianthus superbus L against influenza virus infection- In vitro and in silico biochemical and toxicological screening.

探讨石菖蒲槲皮素 3-葡萄糖苷抗流感病毒感染的作用-体外和计算机生物化学和毒理学筛选。

  • 影响因子:3.78
  • DOI:10.1016/j.fct.2019.110985
  • 作者列表:"Nile SH","Kim DH","Nile A","Park GS","Gansukh E","Kai G
  • 发表时间:2020-01-01
Abstract

:Investigation of antiviral and cytotoxic effect of quercetin 3-glucoside (Q3G) from Dianthus superbus L over influenza virus infection and replication were studied. Moreover, anti-influenza mechanism was screened by time-dependent antiviral assay, virus-induced symptoms and related gene expressions. The blockade of cap-binding domain of polymerase basic protein subunit were analysed by molecular docking study. The Q3G demonstrated potent antiviral activity showing 4.93, 6.43, 9.94, 8.3, and 7.1 μg/mL of IC50 for A/PR/8/34, A/Victoria/3/75, A/WS/33, B/Maryland/1/59, and B/Lee/40, respectively. The cellular toxicity of Q3G and oseltamivir (control) were tested and >100 μg/mL of CC50 value considered as nontoxic. Influenza A virus infection induced a higher ROS production, however potentially reduced by Q3G treatment and significantly blocked virus infection induced acidic vesicular organelles (AVO). Moreover, Q3G has no inhibitory effect for neuraminidase activity but blocked virus replication through time dependent assay and showed more competitive binding affinity (-8.0 kcal/mal) than GTP (-7.0 kcal/mol) to block polymerase basic protein-2 subunit of influenza virus. Q3G from D. superbus showed potent antiviral activity against influenza A and B viruses with suppressive effect on virus-induced cellular ROS generation and AVO formation. Thus, this study provided a new line of research for Q3G to develop possible natural anti-influenza drug.

摘要

研究了石菖蒲槲皮素 3-葡萄糖苷 (Q3G) 对流感病毒感染和复制的抗病毒和细胞毒作用。此外,通过时间依赖性抗病毒试验、病毒诱导症状和相关基因表达筛选抗流感机制。通过分子对接研究分析聚合酶碱性蛋白亚基帽结合域的阻断。Q3G 表现出强大的抗病毒活性,显示 4.93,6.43,9.94,8.3 和 7.1 μ g/mL 的 IC50 为 A/PR/8/34,A/Victoria/3/75,分别为 A/WS/33 、 B/Maryland/1/59 和 B/Lee/40。Q3G 和奥司他韦 (对照) 的细胞毒性进行了测试,并> 100 μ g/mL 的 CC50 值被认为是无毒的。甲型流感病毒感染诱导了较高的 ROS 产生,然而通过 Q3G 处理可能减少,并显著阻断病毒感染诱导的酸性囊泡细胞器 (AVO)。此外,Q3G 对神经氨酸酶活性没有抑制作用,但通过时间依赖性试验阻断病毒复制,并表现出比 GTP (-8.0 kcal/mol) 更竞争性的结合亲和力 (-7.0 kcal/mal)。阻断流感病毒的聚合酶碱性蛋白-2 亚单位。来自 D. superbus 的 Q3G 显示出对甲型和乙型流感病毒 es 的强效抗病毒活性,对病毒诱导的细胞 ROS 生成和 AVO 形成具有抑制作用。因此,本研究为 Q3G 开发可能的天然抗流感药物提供了新的研究路线。

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发表时间:2020-01-19
DOI:10.1093/cid/ciaa050
作者列表:["Baum U","Kulathinal S","Auranen K","Nohynek H"]

METHODS:BACKGROUND:From 2015/16 through 2017/18, injectable, trivalent inactivated influenza vaccines (IIV3) and a nasal spray, tetravalent live-attenuated influenza vaccine (LAIV4) were used in parallel in Finland. To understand how well vaccination with each vaccine type protected children against influenza under real-life conditions, vaccine effectiveness in two-year-olds was estimated for all three seasons. METHODS:Each season, a nationwide register-based cohort study was conducted. The study population comprised 60,088 children in 2015/16, 60,860 children in 2016/17 and 60,345 children in 2017/18. Laboratory-confirmed influenza was the study outcome. Seasonal influenza vaccination with either LAIV4 or IIV3 was the time-dependent exposure of interest. Vaccine effectiveness was defined as 1 minus the hazard ratio comparing vaccinated with unvaccinated children. RESULTS:From 2015/16 through 2017/18, the effectiveness of LAIV4 against influenza of any virus type was estimated at 54.2% (95% confidence interval, 32.2%-69.0%), 20.3% (-12.7% to 43.6%) and 30.5% (10.9%-45.9%); the corresponding effectiveness of IIV3 was 77.2% (48.9%-89.8%), 24.5% (-29.8% to 56.1%) and -20.1% (-61.5% to 10.7%). Neither of the influenza vaccines clearly excelled in protecting children. The LAIV4 effectiveness against type B was greater than against type A and greater than the IIV3 effectiveness against type B. CONCLUSIONS:To understand how influenza vaccines could be improved, vaccine effectiveness must be analyzed by vaccine and virus type. Effectiveness estimates expressing also overall protection levels are needed to guide individual and programmatic decision-making processes. Supported by this analysis, the vaccination program in Finland now recommends LAIV4 and injectable, tetravalent inactivated influenza vaccines replacing IIV3.

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影响因子:1.36
发表时间:2020-01-20
DOI:10.1111/1348-0421.12775
作者列表:["Ainai A","van Riet E","Ito R","Ikeda K","Senchi K","Suzuki T","Tamura SI","Asanuma H","Odagiri T","Tashiro M","Kurata T","Multihartina P","Setiawaty V","Andriana Pangesti KN","Hasegawa H"]

METHODS::Intranasally administered influenza vaccines could be more effective than injected vaccines, since intranasal vaccination can induce virus-specific IgA antibodies in the upper respiratory tract, which is the initial site of infection. In the current study, immune responses elicited by an intranasal inactivated H5 influenza vaccine were evaluated in healthy H5 influenza virus-naive individuals. Three doses of intranasal inactivated whole-virion H5 influenza vaccine induced strong neutralizing nasal IgA and serum IgG antibodies. In addition, a mucoadhesive excipient, carboxy-vinyl polymer (CVP), had a notable impact on the induction of nasal IgA antibody responses but not serum IgG antibody responses. The nasal hemagglutinin (HA)-specific IgA antibody responses clearly correlated with mucosal neutralizing antibody responses, indicating that measurement of nasal HA-specific IgA titers could be used as a surrogate for the mucosal antibody response. Furthermore, increased numbers of plasma cells and vaccine antigen-specific helper T (Th) cells in the peripheral blood were observed after vaccination, suggesting that peripheral blood biomarkers may also be used to evaluate the intranasal vaccine-induced immune response. However, peripheral blood immune cell responses correlated with neutralizing antibody titers in serum samples but not in nasal wash samples. Thus, analysis of the peripheral blood immune response could be a surrogate for the systemic immune response to intranasal vaccination but not for the mucosal immune response. The current study suggests the clinical potential of intranasal inactivated vaccines against H5 influenza viruses and highlights the need to develop novel means to evaluate intranasal vaccine-induced mucosal immune responses. This article is protected by copyright. All rights reserved.

影响因子:6.53
发表时间:2020-01-21
DOI:10.1016/S1473-3099(19)30584-5
作者列表:["Liebowitz D","Gottlieb K","Kolhatkar NS","Garg SJ","Asher JM","Nazareno J","Kim K","McIIwain DR","Tucker SN"]

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