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https://www.readbyqxmd.com/read/29159346/peramivir-analogues-bearing-hydrophilic-side-chains-exhibit-higher-activities-against-h275y-mutant-than-wild-type-influenza-virus
#1
Din-Chi Chiu, Tzu-Chen Lin, Wen-I Huang, Ting-Jen Cheng, Keng-Chang Tsai, Jim-Min Fang
Peramivir is an effective anti-influenza drug in the clinical treatment of influenza, but its efficacy toward the H275Y mutant is reduced. The previously reported cocrystal structures of inhibitors in the mutant neuraminidase (NA) suggest that the hydrophobic side chain should be at the origin of reduced binding affinity. In contrast, zanamivir having a hydrophilic glycerol side chain still possesses high affinity toward the H275Y NA. We thus designed five peramivir analogues (5-9) carrying hydrophilic glycol or glycerol side chains, and evaluated their roles in anti-influenza activity, especially for the H275Y mutant...
November 21, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29156573/neuraminidase-inhibitory-activity-and-constituent-characterization-of-fagopyrum-dibotrys
#2
Xiang Zhang, Yu Cao, Jinhua Li, Ailin Liu, Haibo Liu, Linfang Huang
This study aimed to identify a new biological activity of the widely distributed species Fagopyrum dibotrys. Four F. dibotrys extracts (ethyl acetate (EA), petroleum ether (P), ethanol (E), and water (W)) were explored for their anti-neuraminidase (NA) activity. A total of 32 compounds were identified using UHPLC-Q-Exactive Orbitrap HRMS in the EA extract, which had the best NA inhibitory effects. We used the docking data for supporting compounds' anti-neuraminidase activity. Among them, five compounds including one flavonoid, three organic acids, and one glucoside were discovered for the first time in F...
November 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29153777/vaccination-with-a-human-parainfluenza-virus-type-3-chimeric-fhn-glycoprotein-formulated-with-a-combination-adjuvant-induces-protective-immunity
#3
R Garg, R Brownlie, L Latimer, V Gerdts, A Potter, S van Drunen Littel-van den Hurk
Human parainfluenza virus type 3 (PIV3) is a major cause of lower respiratory disease i.e. bronchitis, bronchiolitis or pneumonia, in infants and young children. Presently there is no licensed vaccine against PIV3. To produce an effective subunit vaccine, a chimeric FHN glycoprotein consisting of the N-terminal ectodomain of the fusion (F) protein linked to the haemagglutinin-neuraminidase (HN) protein without transmembrane domain, and secreted forms of the individual F and HN glycoproteins, were expressed in mammalian cells and purified...
November 16, 2017: Vaccine
https://www.readbyqxmd.com/read/29152877/rapid-risk-assessment-during-the-early-weeks-of-the-2015-2016-influenza-season-in-ukraine
#4
Sophie Newitt, Alla Mironenko, Olha Holubka, Oleksandr Zaika, Olga Gubar, Katri Jalava, Caroline Brown, Iryna Demchyshyna, Tetiana Dykhanovska
BACKGROUND: Several eastern European countries reported a severe influenza season to the World Health Organization (WHO) during late 2015. A country-specific rapid risk assessment for Ukraine was conducted to assess the season's severity and inform public health action.. METHODS: The exposure and hazard were assessed using acute respiratory infection (ARI), severe acute respiratory infection (SARI), laboratory surveillance, virological and vaccine data from weeks 40/2015 to 7/2016 with comparison to four previous seasons to describe the influenza season start (five week consecutive increase in ARI or SARI),, predominant virus types, geographical spread and affected age groups ...
November 20, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/29149072/different-inhibitory-potencies-of-oseltamivir-carboxylate-zanamivir-and-several-tannins-on-bacterial-and-viral-neuraminidases-as-assessed-in-a-cell-free-fluorescence-based-enzyme-inhibition-assay
#5
Stefanie Quosdorf, Anja Schuetz, Herbert Kolodziej
Neuraminidaseis a key enzyme in the life cycle of influenza viruses and is present in some bacterial pathogens. We here assess the inhibitory potency of plant tannins versus clinically used inhibitors on both a viral and a bacterial model neuraminidase by applying the 2'-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid (MUNANA)-based activity assay. A range of flavan-3-ols, ellagitannins and chemically defined proanthocyanidin fractions was evaluated in comparison to oseltamivir carboxylate and zanamivir for their inhibitory activities against viral influenza A (H1N1) and bacterial Vibrio cholerae neuraminidase (VCNA)...
November 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29145498/antigenicity-of-the-2015-2016-seasonal-h1n1-human-influenza-virus-ha-and-na-proteins
#6
Amelia M Clark, Marta L DeDiego, Christopher S Anderson, Jiong Wang, Hongmei Yang, Aitor Nogales, Luis Martinez-Sobrido, Martin S Zand, Mark Y Sangster, David J Topham
Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) influenza virus proteins contributes to reduced vaccine efficacy. To analyze antigenic drift in human seasonal H1N1 viruses derived from the 2009 pandemic H1N1 virus (pH1N1-like viruses) accounts for the limited effectiveness (around 40%) of vaccination against pH1N1-like viruses during the 2015-2016 season, nasal washes/swabs collected from adult subjects in the Rochester, NY area, were used to sequence and isolate the circulating viruses. The HA and NA proteins from viruses circulating during the 2015-2016 season encoded eighteen and fourteen amino acid differences, respectively, when compared to A/California/04/2009, a strain circulating at the origin of the 2009 pandemic...
2017: PloS One
https://www.readbyqxmd.com/read/29141777/design-synthesis-and-biological-evaluation-of-novel-oseltamivir-derivatives-as-potent-neuraminidase-inhibitors
#7
Zhen Wang, Li Ping Cheng, Xing Hua Zhang, Wan Pang, Liang Li, Jin Long Zhao
Neuraminidase (NA) is one of the particular potential targets for novel antiviral therapy. In this work, a series of neuraminidase inhibitors with the cyclohexene scaffold were studied based upon the combination of 3D-QSAR, molecular docking, and molecular dynamics techniques. The results indicate that the built 3D-QSAR models yield reliable statistical information: the correlation coefficient (r(2)) and cross-validation coefficient (q(2)) of CoMFA (comparative molecular field analysis) are 0.992 and 0.819; the r(2) and q(2) of CoMSIA (comparative molecular similarity analysis) are 0...
November 4, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29139346/in-vivo-mallard-experiments-indicate-that-zanamivir-has-less-potential-for-environmental-influenza-a-virus-resistance-development-than-oseltamivir
#8
Marie Nykvist, Anna Gillman, Hanna Söderström Lindström, Chaojun Tang, Ganna Fedorova, Åke Lundkvist, Neus Latorre-Margalef, Michelle Wille, Josef D Järhult
Neuraminidase inhibitors are a cornerstone of influenza pandemic preparedness before vaccines can be mass-produced and thus a neuraminidase inhibitor-resistant pandemic is a serious threat to public health. Earlier work has demonstrated the potential for development and persistence of oseltamivir resistance in influenza A viruses exposed to environmentally relevant water concentrations of the drug when infecting mallards, the natural influenza reservoir that serves as the genetic base for human pandemics. As zanamivir is the major second-line neuraminidase inhibitor treatment, this study aimed to assess the potential for development and persistence of zanamivir resistance in an in vivo mallard model; especially important as zanamivir will probably be increasingly used...
November 15, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29138445/inhibition-activity-of-a-traditional-chinese-herbal-formula-huang-lian-jie-du-tang-and-its-major-components-found-in-its-plasma-profile-on-neuraminidase-1
#9
Xuelin Zhou, Haotian Li, Zhilong Shi, Sijia Gao, Shizhang Wei, Kun Li, Jiabo Wang, Jianyu Li, Ruilin Wang, Man Gong, Yanling Zhao, Xiaohe Xiao
Huang-Lian-Jie-Du-Tang (HLJDT), a traditional formula with four TCM herbs, has been used for hundred years for different diseases. The current study aimed to assess the inhibitory activity of HLJDT against H1N1 neuraminidase (NA-1), and identify potent NA-1 inhibitors from its plasma profile. The in vitro NA-1 study has shown that the water extract of HLJDT potently inhibited NA-1 (IC50 = 112.6 μg/ml; Ki = 55.6 μg/ml) in a competitive mode. The IC50 values of the water extracts of its four herbs were as follows: Coptidis Rhizoma, 96...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137330/virtual-screening-approach-to-identifying-influenza-virus-neuraminidase-inhibitors-using-molecular-docking-combined-with-machine-learning-based-scoring-function
#10
Li Zhang, Hai-Xin Ai, Shi-Meng Li, Meng-Yuan Qi, Jian Zhao, Qi Zhao, Hong-Sheng Liu
In recent years, an epidemic of the highly pathogenic avian influenza H7N9 virus has persisted in China, with a high mortality rate. To develop novel anti-influenza therapies, we have constructed a machine-learning-based scoring function (RF-NA-Score) for the effective virtual screening of lead compounds targeting the viral neuraminidase (NA) protein. RF-NA-Score is more accurate than RF-Score, with a root-mean-square error of 1.46, Pearson's correlation coefficient of 0.707, and Spearman's rank correlation coefficient of 0...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135323/impact-assessment-of-the-rational-selection-of-training-and-test-sets-on-the-predictive-ability-of-qsar-models
#11
M F Andrada, E G Vega-Hissi, M R Estrada, J C Garro Martinez
This study performed an analysis of the influence of the training and test set rational selection on the quality and predictively of the quantitative structure-activity relationship (QSAR) model. The study was carried out on three different datasets of Influenza Neuraminidase (H1N1) inhibitors. The three datasets were divided into training and test sets using three rational selection methods: based on k-means, Kennard-Stone algorithm and Activity and the results were compared with Random selection. Then, a total of 31,490 mathematical models were developed and those models that presented a determination coefficient higher than: r(2)train > 0...
November 14, 2017: SAR and QSAR in Environmental Research
https://www.readbyqxmd.com/read/29134205/towards-the-electrochemical-diagnostic-of-influenza-virus-development-of-a-graphene-au-hybrid-nanocomposite-modified-influenza-virus-biosensor-based-on-neuraminidase-activity
#12
Ülkü Anik, Yudum Tepeli, Maher Sayhi, Jihene Nsiri, Mohamed Fethi Diouani
An effective electrochemical influenza A biosensor based on a graphene-gold (Au) hybrid nanocomposite modified Au-screen printed electrode has been developed. The working principle of the developed biosensor relies on the measurement of neuraminidase (N) activity. After the optimization of experimental parameters like the effect of bovine serum albumin addition and immobilization times of fetuin A and PNA lectin, the analytical characteristics of the influenza A biosensor were investigated. As a result, a linear range between 10(-8) U mL(-1) and 10(-1) U mL(-1) was found with a relative standard deviation value of 3...
November 14, 2017: Analyst
https://www.readbyqxmd.com/read/29121959/why-european-and-united-states-drug-regulators-are-not-speaking-with-one-voice-on-anti-influenza-drugs-regulatory-review-methodologies-and-the-importance-of-deep-product-reviews
#13
Shai Mulinari, Courtney Davis
BACKGROUND: Relenza represents the first neuraminidase inhibitor (NI), a class of drugs that also includes the drug Tamiflu. Although heralded as breakthrough treatments in influenza, NI efficacy has remained highly controversial. A key unsettled question is why the United States Food and Drug Administration (FDA) has approved more cautious efficacy statements in labelling than European regulators for both drugs. METHODS: We conducted a qualitative analysis of United States and European Union regulatory appraisals for Relenza to investigate the reasons for divergent regulatory interpretations, pertaining to Relenza's capacity to alleviate symptoms and reduce frequency of complications of influenza...
November 9, 2017: Health Research Policy and Systems
https://www.readbyqxmd.com/read/29118122/unique-directional-motility-of-influenza-c-virus-controlled-by-its-filamentous-morphology-and-short-range-motions
#14
Tatsuya Sakai, Hiroaki Takagi, Yasushi Muraki, Mineki Saito
Influenza virus motility is based on cooperation between two viral spike proteins, hemagglutinin (HA) and neuraminidase (NA), and is a major determinant of virus infectivity. To translocate a virus particle on the cell surface, HA molecules exchange viral receptors and NA molecules accelerate the receptor exchange of HA. This type of virus motility was recently identified in influenza A virus (IAV). To determine if other influenza virus types have a similar receptor-exchange mechanism-driven motility, we investigated influenza C virus (ICV) motility on a receptor-fixed glass surface...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29117669/late-diagnosis-of-influenza-in-adult-patients-during-a-seasonal-outbreak
#15
Seong-Ho Choi, Jin-Won Chung, Tark Kim, Ki-Ho Park, Mi Suk Lee, Yee Gyung Kwak
Background/Aims: Due to advances in diagnostic techniques, clinicians are more frequently performing influenza diagnostic tests and referring to their test results ahead of the administration of neuraminidase inhibitors (NAIs). To investigate the clinical significance of the time from symptom onset to laboratory diagnosis, we reviewed the clinical characteristics of adult patients with influenza who had an early laboratory diagnosis (ED) or a late laboratory diagnosis (LD) at one of four tertiary care centers during a seasonal outbreak of influenza...
November 10, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29113775/spread-of-predominant-neuraminidase-and-hemagglutinin-co-mutations-in-the-influenza-a-h3n2-virus-genome
#16
Yong Chong, Hideyuki Ikematsu
Genetic variation of influenza neuraminidase (NA), unlike for hemagglutinin (HA), has not been fully characterized. Therefore, we determined the relation between mutations in the NA and HA genome segments of 205 influenza A/H3N2 viruses isolated from patients in Japan during the five seasons from 2010 to 2015. The amino acid (AA) sequences of the NA and HA proteins in these isolates were then determined. In the 2011-2012 season, there was the emergence of isolates with NA and HA sequences containing AA93G (NA93G) and AA278K (HA278K), respectively (24/48 isolates, 50...
November 4, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29112968/fitness-cost-of-reassortment-in-human-influenza
#17
Mara Villa, Michael Lässig
Reassortment, which is the exchange of genome sequence between viruses co-infecting a host cell, plays an important role in the evolution of segmented viruses. In the human influenza virus, reassortment happens most frequently between co-existing variants within the same lineage. This process breaks genetic linkage and fitness correlations between viral genome segments, but the resulting net effect on viral fitness has remained unclear. In this paper, we determine rate and average selective effect of reassortment processes in the human influenza lineage A/H3N2...
November 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29107426/synthesis-and-biological-evaluation-of-nh2-acyl-oseltamivir-analogues-as-potent-neuraminidase-inhibitors
#18
Kuanglei Wang, Fei Yang, Lihui Wang, Kemin Liu, Lu Sun, Bin Lin, Yaping Hu, Boyu Wang, Maosheng Cheng, Yongshou Tian
Neuraminidase inhibitors can deter nascent viruses from infecting intact cells by preventing their release from host cells. Herein, a neuraminidase inhibitor 11b absent of basic moieties was discovered in the process of searching for inhibitors targeting 150 cavity. It exhibited potent inhibitions against wild-type neuraminidases from group 1 (H5N1 and H1N1) and group 2 (H7N9) subtypes with IC50 values similar to those of oseltamivir carboxylate. Moreover, 11b showed moderate inhibitions against mutant neuraminidases from H5N1-H274Y and H1N1-H274Y with IC50 values of 2075 nM and 1382 nM, which were inferior to those of oseltamivir carboxylate (6095 nM and 4071 nM)...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29104094/a-two-year-monitoring-period-of-the-genetic-properties-of-clade-2-3-2-1c-h5n1-viruses-in-nigeria-reveals-the-emergence-and-co-circulation-of-distinct-genotypes
#19
Agnes Laleye, Tony Joannis, Ismaila Shittu, Clement Meseko, Gianpiero Zamperin, Adelaide Milani, Bianca Zecchin, Alice Fusaro, Isabella Monne, Celia Abolnik
Phylogenetic analyses of the complete genomes of the highly pathogenic avian influenza (HPAI) 2.3.2.1c H5N1 virus strains causing outbreaks in Nigeria's poultry population from 2014 to 2016 showed evidence of distinct co-circulating genotypes and the emergence of reassortant viruses. One of these reassortants became the predominant strain by 2016, and the NA protein of this strain possessed the V96A substitution known to confer reduced susceptibility to neuraminidase inhibiting antiviral drugs. Our findings also demonstrated evolutionary relationships between Nigerian isolates and European and Middle Eastern strains of H5N1 which provides further evidence for the proposed role of migratory birds in spreading the virus, although the involvement of the live poultry trade cannot be excluded...
November 15, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29100932/evolution-of-equine-influenza-viruses-h3n8-during-a-brazilian-outbreak-2015
#20
Patricia Filippsen Favaro, Wilson Roberto Fernandes, Dilmara Reischak, Paulo Eduardo Brandão, Sheila Oliveira de Souza Silva, Leonardo José Richtzenhain
Equine influenza is one of the major respiratory infectious diseases in horses. An equine influenza virus outbreak was identified in vaccinated and unvaccinated horses in a veterinary school hospital in São Paulo, SP, Brazil, in September 2015. The twelve equine influenza viruses isolated belonged to Florida Clade 1. The hemagglutinin and neuraminidase amino acid sequences were compared with the recent isolates from North and South America and the World Organisation for Animal Health recommended Florida Clade 1 vaccine strain...
October 13, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
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