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https://www.readbyqxmd.com/read/28448045/fluorescence-based-neuraminidase-inhibition-assay-to-assess-the-susceptibility-of-influenza-viruses-to-the-neuraminidase-inhibitor-class-of-antivirals
#1
Sook-Kwan Leang, Aeron C Hurt
The neuraminidase (NA) inhibitors are the only class of antivirals approved for the treatment and prophylaxis of influenza that are effective against currently circulating strains. In addition to their use in treating seasonal influenza, the NA inhibitors have been stockpiled by a number of countries for use in the event of a pandemic. It is therefore important to monitor the susceptibility of circulating influenza viruses to this class of antivirals. There are different types of assays that can be used to assess the susceptibility of influenza viruses to the NA inhibitors, but the enzyme inhibition assays using either a fluorescent substrate or a chemiluminescent substrate are the most widely used and recommended...
April 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28446666/mouse-saliva-inhibits-transit-of-influenza-virus-to-the-lower-respiratory-tract-by-efficiently-blocking-influenza-neuraminidase-activity
#2
Brad Gilbertson, Wy Ching Ng, Simon Crawford, Jenny L McKimm-Breschkin, Lorena E Brown
We have previously identified a novel inhibitor of influenza virus in mouse saliva that halts the progression of susceptible viruses from the upper to the lower respiratory tract of mice in vivo and neutralizes viral infectivity in MDCK cells. Here, we investigated the viral target of the salivary inhibitor by using reverse genetics to create hybrid viruses with some surface proteins derived from an inhibitor-sensitive strain and others from an inhibitor-resistant strain. These viruses demonstrated that the origin of the viral neuraminidase (NA), but not the hemagglutinin or matrix proteins, was the determinant of susceptibility to the inhibitor...
April 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28442549/neuraminidases-3-and-4-regulate-neuronal-function-by-catabolizing-brain-gangliosides
#3
Xuefang Pan, Camila De Britto Pará De Aragão, Juan P Velasco-Martin, David A Priestman, Harry Y Wu, Kohta Takahashi, Kazunori Yamaguchi, Luisella Sturiale, Domenico Garozzo, Frances M Platt, Nathalie Lamarche-Vane, Carlos R Morales, Taeko Miyagi, Alexey V Pshezhetsky
Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains...
April 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28438112/h3n2-canine-influenza-virus-infection-in-a-dog
#4
C E Watson, C Bell, K Toohey-Kurth
In 2015, H3N2 canine influenza emerged in dogs in the greater Chicago area. During this time, a 10-year-old German Shepherd dog presented to the referring veterinarian with lethargy and coughing that quickly progressed to death. This report describes the macroscopic and microscopic lesions and the molecular testing performed to identify the novel North American H3N2 strain of canine influenza. The larynx, pharynx, and trachea were covered by a fibrinonecrotic membrane. Bilaterally, the lungs had multifocal subpleural necrosis of the caudal lung lobes with hemorrhage, congestion, and pulmonary edema...
May 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28435701/crystal-structure-of-2e-3-4-di-methyl-amino-phen-yl-1-thio-phen-2-yl-prop-2-en-1-one
#5
Gabriela Porto de Oliveira, Leandro Bresolin, Darlene Correia Flores, Renan Lira de Farias, Adriano Bof de Oliveira
The equimolar reaction between 4-(di-methyl-amino)-benzaldehyde and 2-acetyl-thio-phene in basic ethano-lic solution yields the title compound, C15H15NOS, whose mol-ecular structure matches the asymmetric unit. The mol-ecule is not planar, the dihedral angle between the aromatic and the thio-phene rings being 11.4 (2)°. In the crystal, mol-ecules are linked by C-H⋯O and weak C-H⋯S inter-actions along [100], forming R2(2) (8) rings, and by weak C-H⋯O inter-actions along [010], forming chains with a C(6) graph-set motif...
April 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28426220/fluorescent-neuraminidase-assay-based-on-supramolecular-dye-capture-after-enzymatic-cleavage
#6
Wenqi Liu, César F A Gómez-Durán, Bradley D Smith
A conceptually new type of enzymatic cleavage assay is reported that utilizes in-situ supramolecular capture of the fluorescent product. A squaraine-derived substrate with large blocking groups at each end of its structure cannot be threaded by a tetralactam macrocycle until the blocking groups are removed by enzyme cleavage. A prototype design responds to viral neuraminidase, an indicator of influenza infection, and also measures susceptibility of the sample to neuraminidase inhibitor drugs. The substrate structure incorporates three key features; (a) a bis(4-amino-3-hydroxyphenyl)squaraine core with bright deep-red fluorescence and excellent photostability, (b) an N-methyl group at each end of the squaraine core that ensures fast macrocycle threading kinetics, and (c) sialic acid blocking groups that prevent macrocycle threading until they are removed by viral neuraminidase...
April 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28417272/early-administration-of-neuraminidase-inhibitors-in-adult-patients-hospitalized-for-influenza-does-not-benefit-survival-a-retrospective-cohort-study
#7
S-H Choi, T Kim, K-H Park, Y G Kwak, J-W Chung, M S Lee
The administration of neuraminidase inhibitors (NAIs) within 2 days after the onset of symptoms (early NAI therapy) has been shown to reduce mortality in adult patients with severe influenza. However, there is no sufficiently solid evidence supporting the effectiveness of early NAI therapy on mortality. We reviewed the clinical data from 506 adult patients who were hospitalized for influenza between March 2010 and March 2014, to investigate the impact of early NAI therapy on mortality. Nearly one-third of the study patients were infected with influenza B (influenza A, influenza B, and co-infection of both in 68...
April 18, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28410396/evolution-of-the-neuraminidase-gene-of-seasonal-influenza-a-and-b-viruses-in-thailand-between-2010-and-2015
#8
Nipaporn Tewawong, Preeyaporn Vichiwattana, Sumeth Korkong, Sirapa Klinfueng, Nungruthai Suntronwong, Thanunrat Thongmee, Apiradee Theamboonlers, Sompong Vongpunsawad, Yong Poovorawan
The neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are commonly used for the treatment and control of influenza A and B virus infection. However, the emergence of new influenza virus strains with reduced susceptibility to NAIs may appear with the use of these antivirals or even naturally. We therefore screened the neuraminidase (NA) sequences of seasonal influenza virus A(H1N1), A(H1N1)pdm09, A(H3N2), and influenza B virus strains identified in Thailand for the presence of substitutions previously reported to reduce susceptibility to NAIs...
2017: PloS One
https://www.readbyqxmd.com/read/28405632/evidence-of-intercontinental-spread-and-uncommon-variants-of-low-pathogenicity-avian-influenza-viruses-in-ducks-overwintering-in-guatemala
#9
Ana S Gonzalez-Reiche, Martha I Nelson, Mathew Angel, Maria L Müller, Lucia Ortiz, Jayeeta Dutta, Harm van Bakel, Celia Cordon-Rosales, Daniel R Perez
Over a hundred species of aquatic birds overwinter in Central America's wetlands, providing opportunities for the transmission of influenza A viruses (IAVs). To date, limited IAV surveillance in Central America hinders our understanding of the evolution and ecology of IAVs in migratory hosts within the Western Hemisphere. To address this gap, we sequenced the genomes of 68 virus isolates obtained from ducks overwintering along Guatemala's Pacific Coast during 2010 to 2013. High genetic diversity was observed, including 9 hemagglutinin (HA) subtypes, 7 neuraminidase (NA) subtypes, and multiple avian IAV lineages that have been detected at low levels (<1%) in North America...
March 2017: MSphere
https://www.readbyqxmd.com/read/28402019/epigallocatechin-gallate-inhibits-streptococcus-pneumoniae-virulence-by-simultaneously-targeting-pneumolysin-and-sortase%C3%A2-a
#10
Meng Song, Zihao Teng, Meng Li, Xiaodi Niu, Jianfeng Wang, Xuming Deng
Streptococcus pneumoniae (pneumococcus), the causative agent of several human diseases, possesses numerous virulence factors associated with pneumococcal infection and pathogenesis. Pneumolysin (PLY), an important virulence factor, is a member of the cholesterol-dependent cytolysin family and has cytolytic activity. Sortase A (SrtA), another crucial pneumococcal virulence determinate, contributes greatly to the anchoring of many virulence-associated surface proteins to the cell wall. In this study, epigallocatechin gallate (EGCG), a natural compound with little known antipneumococcal activity, was shown to directly inhibit PLY-mediated haemolysis and cytolysis by blocking the oligomerization of PLY and simultaneously reduce the peptidase activity of SrtA...
April 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28400751/ethanolic-extract-of-melia-fructus-has-anti-influenza-a-virus-activity-by-affecting-viral-entry-and-viral-rna-polymerase
#11
Young-Hee Jin, Jang-Gi Choi, Won-Kyung Cho, Jin Yeul Ma
Meliae Fructus (MF) is the dried ripe fruit of Melia toosendan Siebold et Zuccarini, Meliaceae family. MF is widely used in traditional medicine to treat inflammation and helminthic infection and has anti-bacterial, anti-oxidant, anti-cancer, anti-inflammatory, and analgesic activities. However, potential anti-influenza properties of MF have yet to be investigated. We determined whether an ethanolic extract of MF (EMF) has anti-viral activity via an EMF pre-, co-, and post-treatment assay, using the Influenza A/PR/8/34 and H3N2 virus on Madin-Darby canine kidney (MDCK) cells...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28393840/antiviral-activity-of-chlorogenic-acid-against-influenza-a-h1n1-h3n2-virus-and-its-inhibition-of-neuraminidase
#12
Yue Ding, Zeyu Cao, Liang Cao, Gang Ding, Zhenzhong Wang, Wei Xiao
Lonicera japonica Thunb, rich in chlorogenic acid (CHA), is used for viral upper respiratory tract infection treatment caused by influenza virus, parainfluenza virus, and respiratory syncytial virus, ect in China. It was reported that CHA reduced serum hepatitis B virus level and death rate of influenza virus-infected mice. However, the underlying mechanisms of CHA against the influenza A virus have not been fully elucidated. Here, the antiviral effects and potential mechanisms of CHA against influenza A virus were investigated...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28386784/genetic-analysis-of-a-novel-reassortant-h11n9-isolated-from-waterfowl-in-south-korea-in-2016
#13
Tran Bac Le, In Hong Lee, Hyun Soo Kim, Seung Kyoo Oh, Sang Heui Seo
Aquatic birds are known to harbor all the known influenza A viruses. In the winter of January 2016, we surveyed influenza A virus in the feces of migratory birds in South Korea. The novel re-assorted H11N9 avian influenza virus, which contains genes from avian influenza viruses of poultry and wild birds, was isolated. The polymerase basic 2 (PB2), polymerase basic 1 (PB1), hemagglutinin (HA), and nucleoprotein (NP) genes were most closely related to those of domestic duck-origin avian influenza viruses, while the non-structural (NS) gene was closely related to that of domestic goose-origin avian influenza virus...
April 6, 2017: Virus Genes
https://www.readbyqxmd.com/read/28385598/discovery-of-acylguanidine-oseltamivir-carboxylate-derivatives-as-potent-neuraminidase-inhibitors
#14
Zhaoliang Li, Yanchun Meng, Shengtao Xu, Wang Shen, Zhaoqing Meng, Zhenzhong Wang, Gang Ding, Wenzhe Huang, Wei Xiao, Jinyi Xu
In search of novel anti-influenza agents with higher potency, a series of acylguanidine oseltamivir carboxylate analogues were synthesized and evaluated against influenza viruses (H1N1 and H3N2) in vitro. The representative compounds with strong inhibitory activities (IC50 <40nM) against neuraminidase (NA) were further tested against the NA from oseltamivir-resistant strain (H259Y). Among them, compounds 9 and 17 were potent NA inhibitors that exhibited a 5 and 11-fold increase in activity comparing with oseltamivir carboxylate (2, OC) against the H259Y mutant, respectively...
May 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28384330/correction-neuraminidase-inhibitors-and-hospital-mortality-in-british-patients-with-h1n1-influenza-a-a-re-analysis-of-observational-data
#15
Martin Wolkewitz, Martin Schumacher
[This corrects the article DOI: 10.1371/journal.pone.0160430.].
2017: PloS One
https://www.readbyqxmd.com/read/28382157/progress-of-small-molecular-inhibitors-in-the-development-of-anti-influenza-virus-agents
#16
REVIEW
Xiaoai Wu, Xiuli Wu, Qizheng Sun, Chunhui Zhang, Shengyong Yang, Lin Li, Zhiyun Jia
The influenza pandemic is a major threat to human health, and highly aggressive strains such as H1N1, H5N1 and H7N9 have emphasized the need for therapeutic strategies to combat these pathogens. Influenza anti-viral agents, especially active small molecular inhibitors play important roles in controlling pandemics while vaccines are developed. Currently, only a few drugs, which function as influenza neuraminidase (NA) inhibitors and M2 ion channel protein inhibitors, are approved in clinical. However, the acquired resistance against current anti-influenza drugs and the emerging mutations of influenza virus itself remain the major challenging unmet medical needs for influenza treatment...
2017: Theranostics
https://www.readbyqxmd.com/read/28380622/induction-of-broadly-cross-reactive-stalk-specific-antibody-responses-to-influenza-group-1-and-group-2-hemagglutinins-by-natural-h7n9-virus-infection-in-humans
#17
Lu Liu, Raffael Nachbagauer, Lingyan Zhu, Yang Huang, Xinci Xie, Shan Jin, Anli Zhang, Yanmin Wan, Ariana Hirsh, Di Tian, Xiaolin Shi, Zhaoguang Dong, Songhua Yuan, Yunwen Hu, Florian Krammer, Xiaoyan Zhang, Jianqing Xu
Background.: The outbreak of novel avian H7N9 influenza virus infections in China in 2013 has demonstrated the continuing threat posed by zoonotic pathogens. Deciphering the immune response during natural infection will guide future vaccine development. Methods.: We assessed the induction of heterosubtypic cross-reactive antibodies induced by H7N9 infection against a large panel of recombinant hemagglutinins and neuraminidases by quantitative enzyme-linked immunosorbent assay, and novel chimeric hemagglutinin constructs were used to dissect the anti-stalk or -head humoral immune response...
February 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28374582/detection-of-enzyme-inhibitors-in-crude-natural-extracts-using-droplet-based-microfluidics-coupled-to-hplc
#18
Abraham Ochoa, Enrique Álvarez-Bohórquez, Eduardo Castillero, Luis F Olguin
Natural product screening for new bioactive compounds can greatly benefit from low reagents consumption and high throughput capacity of droplet-based microfluidic systems. However, the creation of large droplet libraries in which each droplet carries a different compound is a challenging task. A possible solution is to use an HPLC coupled to a droplet generating microfluidic device to sequentially encapsulate the eluting compounds. In this work we demonstrate the feasibility of carrying out enzyme inhibiting assays inside nano-liter droplets with the different components of a natural crude extract after being separated by a coupled HPLC column...
April 4, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28371325/analysis-of-genetic-variants-of-transferrin-in-human-serum-after-desialylation-by-capillary-zone-electrophoresis-and-capillary-isoelectric-focusing
#19
Jitka Caslavska, Christian Lanz, Patricie Burda, Micha Tobler, Wolfgang Thormann
Capillary electrophoresis analysis of transferrin in human serum is used to assess genetic variants after desialylation with neuraminidase and iron saturation to reduce the complexity of the transferrin pattern and thus facilitate the recognition of transferrin polymorphisms. Asialo-transferrin forms are analyzed by capillary zone electrophoresis using assay conditions as for the monitoring of carbohydrate-deficient transferrin or by capillary isoelectric focusing in a pH 5-8 gradient which requires immunoextraction of transferrin prior to analysis...
March 31, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28365829/newcastle-disease-virus-like-particles-induce-dendritic-cell-maturation-and-enhance-viral-specific-immune-response
#20
Jing Qian, Jiaxin Ding, Renfu Yin, Yixue Sun, Cong Xue, Xiaohong Xu, Jianzhong Wang, Chan Ding, Shengqing Yu, Xiufan Liu, Shunlin Hu, Yanlong Cong, Zhuang Ding
Circulating of genotype VII Newcastle disease virus (NDV) is a great threat to the poultry industry worldwide. Virus-like particles (VLPs) are increasingly being considered as potential viral vaccines due to their safety and efficacy. In this study, we analyzed in vitro the stimulatory effects of VLPs containing the matrix and hemagglutinin-neuraminidase of genotype VII NDV on dendritic cells (DCs) and evaluated their immunogenicity in mice. The results showed that immature bone marrow-derived dendritic cells (BMDCs) responded to stimulation with VLPs by up-regulating expressions of MHC II, CD40, CD80, and CD86 molecules and by increasing the cytokine secretions of TNF-α, IFN-γ, IL-6, and IL-12p70...
April 1, 2017: Virus Genes
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