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排序方式: 共有412条查询结果,搜索用时 46 毫秒
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Analysis of mutations I117V and I117M in the neuraminidase of influenza A pandemic (H1N1) 2009 viruses showed that I117V confers a mild reduction in oseltamivir sensitivity and has a synergistic effect of further increasing resistance when combined with H275Y. Contrary to recent reports, the I117M mutation does not alter oseltamivir sensitivity. 相似文献
44.
We use electron cryotomography to reconstruct virions of two influenza A H3N2 virus strains. The maps reveal the structure of the viral envelope containing hemagglutinin (HA) and neuraminidase (NA) glycoproteins and the virus interior containing a matrix layer and an assembly of ribonucleoprotein particles (RNPs) that package the genome. We build a structural model for the viral surface by locating copies of the X-ray structure of the HA ectodomain into density peaks on the virus surface. We calculate inter-glycoprotein distances and the fractional volume occupied by glycoproteins. The models suggest that for typical HA densities on virus, Fabs can bind to epitopes on the HA stem domain. The models also show how membrane curvature may influence the number of glycoproteins that can simultaneously interact with a target surface of receptors. 相似文献
45.
John S. Oxford 《Influenza and other respiratory viruses》2007,1(1):27-34
Influenza is a highly contagious and debilitating disease that imposes an excess burden of complications and mortality. Antiviral therapy is the primary intervention for treatment and post‐exposure prophylaxis (PEP) of influenza. Amantadine and rimantadine are members of the M2 class of antiviral agents and are moderately effective in influenza management. However, their utility is compromised by high levels of resistance, tolerability concerns and a lack of efficacy against influenza B. An alternative class of agents, the neuraminidase inhibitors (NIs), represent the most advanced form of antiviral therapy available, and act by specifically inhibiting the neuraminidase enzymes that are present on all influenza subtypes. Two NIs, oseltamivir and zanamivir, are currently available for clinical use. Oseltamivir, the most widely used NI, is administered orally as a prodrug (oseltamivir carboxylate) and systemically distributed to all potential infection sites. Zanamivir, a second NI, is administered by inhalation via a disk inhaler and deposited primarily in the respiratory tract. When administered within 48 hours of symptom onset, both agents significantly reduce illness duration and symptom severity, and decrease the rate of influenza‐associated complications. With oseltamivir, greater benefits are detected with earlier treatment initiation (<12 hours). In PEP, both NIs effectively protect the close contacts of index cases from symptomatic influenza. Oseltamivir and zanamivir are generally well tolerated and associated with a low level of resistance. Emerging evidence supports the activity of both NIs against the H5N1avian influenza infection, which is a pandemic candidate. However, the WHO currently recommends the use of oseltamivir for the management of suspected cases, given the systemic nature of the H5N1 challenge. Ongoing studies are exploring the effectiveness of oseltamivir, zanamivir and other NIs for pandemic management. 相似文献
46.
Melkamu Getie‐Kebtie Ishrat Sultana Maryna Eichelberger Michail Alterman 《Influenza and other respiratory viruses》2013,7(4):521-530
Please cite this paper as: Getie‐Kebtie et al. (2012) Label‐free mass spectrometry‐based quantification of hemagglutinin and neuraminidase in influenza virus preparations and vaccines. Influenza and Other Respiratory Viruses 7(4), 521–530. Background Influenza vaccination is the primary method for preventing influenza and its severe complications. An accurate rapid method to determine hemagglutinin (HA) concentration would facilitate reference antigen preparation and consequently expedite availability of seasonal as well as pandemic vaccines. Objective The goal of this study was to develop a label‐free mass spectrometry (MS) based method that enables simultaneous identification and quantification of HA, neuraminidase (NA), and other viral proteins and protein contaminations in influenza vaccine or virus preparations. Methods The method presented is based on LC/MSE analysis of vaccine or virus preparations tryptic digests spiked with a known amount of protein standard from which a universal response factor is generated and applied to calculate the concentration of proteins identified in the mixture. Results We show that, with the use of an appropriate internal standard, the label‐free MS‐based protein quantification method is applicable for simultaneous identification and absolute quantification of HA and identification and relative quantification of other influenza proteins as well as protein impurities in influenza vaccines and virus preparations. We show that different subtype recombinant HA is preferred internal standard that provides the most accurate results in absolute quantification of HAs and other influenza proteins. We applied this method to measure the absolute quantity of HA as well as relative quantities of other viral proteins and impurities in preparations of whole virus and monovalent vaccine, providing data to demonstrate strain‐dependent differences in the amount of NA. Conclusion The label‐free MS method presented here is ideally suited for timely preparation of reference material needed for potency testing of seasonal and pandemic vaccines. 相似文献
47.
《Expert review of anti-infective therapy》2013,11(2):165-167
The novel avian H7N9 influenza virus has caused more than 130 human infections with 43 deaths (as of September, 2013) in China. Because of the lack of existing immunity against H7 subtype influenza viruses in the human population and the absence of a licensed commercial vaccine, antiviral drugs are critical tools for the treatment of infection with this novel H7N9. Both M2-ion channel blockers and neuraminidase inhibitors are used as antiviral drugs for influenza infections of humans. The emerging H7N9 viruses are resistant to the M2-ion channel blockers because of a S31N mutation in the M2 protein; additionally, some H7N9 isolates have gained neuraminidase R292K substitution resulting in broad resistance to neuraminidase inhibitors. In this study we report that Alferon N can inhibit wild type and 292K H7N9 viruses replication in vitro. Since Alferon N is approved for clinical use, this would allow a rapid regulatory approval process for this drug under pandemic threat. 相似文献
48.
《Expert review of anti-infective therapy》2013,11(2):123-143
Peramivir (BioCryst Pharmaceuticals) is a novel investigational intravenous neuraminidase inhibitor that exhibits potent antiviral activity against influenza A and B viruses. Peramivir is created by a structure-based drug design and consists of a cyclopentane backbone with a positively charged guanidinyl group and lipophilic side chains. Peramivir was made available in the USA through the Emergency Investigational New Drug regulations and under an Emergency Use Authorization for hospitalized patients with known or suspected influenza during the 2009 H1N1 influenza pandemic. In trials involving ambulatory adult subjects, intravenous peramivir is safe and has a pharmacokinetic profile that supports once-daily dosing. The drug is licensed in Japan and South Korea and is currently undergoing Phase III trials in the USA. Viral resistance mechanisms to peramivir have not been fully delineated and ongoing surveillance is important. Given the serious health threat of influenza at all ages and limitations in vaccine delivery, peramivir is a promising addition to the currently limited treatment options for the treatment of severe influenza infection. 相似文献
49.
Geertjan Wesseling 《INT J CHRONIC OBSTR》2007,2(1):5-10
Influenza viruses cause respiratory tract infections that in patients with underlying lung diseases such as chronic obstructive pulmonary disease (COPD) are associated with exacerbations and excess morbidity and mortality. Typically, influenza B is associated with relatively mild, local outbreaks, whereas influenza A is the cause of world-wide pandemics. Upon infection, two antigens present on the viral surface, hemagglutinin and neuraminidase result in human immunity, but since many subtypes of these antigens exist that vary over time, immunity in the population is blunted. Vaccination is advocated in high-risk groups including patients with underlying (lung) diseases and in the elderly, and needs to be repeated annually with vaccines expected to cover the expected change in viral antigenicity. When started early, antiviral drugs, especially neuraminidase-inhibitors can be prescribed in adjunct to nonspecific interventions in an attempt to shorten disease duration and to prevent complications in case of an influenza infection. Currently, the effectiveness of antiviral drugs specifically in patients with COPD has not been proven. 相似文献
50.
流感病毒神经氨酸酶抑制剂筛选模型的建立和应用 总被引:9,自引:0,他引:9
目的建立适用于高通量筛选的流感病毒神经氨酸酶(neuraminidase,NA)抑制剂筛选模型。方法从甲型及乙型流感病毒中制备神经氨酸酶,以2′-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid(MUNANA)作为底物,建立检测神经氨酸酶活性的荧光测定法及其抑制剂体外筛选方法,用高通量筛选系统对1 200个化合物与提取物进行初筛。结果神经氨酸酶酶促反应以pH 3.5,二价阳离子浓度为2~6 mmol·L-1及37℃孵育时酶活性最佳;甲、乙型流感病毒不同株神经氨酸酶的米氏常数(Km)的范围为(4.89~5.94) μmol·L-1;初筛发现12个化合物对流感病毒神经氨酸酶有可重复的抑制活性。结论优化了神经氨酸酶反应体系,建立的体外模型可用于抗甲、乙型流感病毒药物的高通量筛选及酶抑制动力学的研究。 相似文献