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influenza a h1n1 pandemic strain evolution--divergence and the potential for antigenic drift variants.the emergence of a novel a(h1n1) strain in 2009 was the first influenza pandemic of the genomic age, and unprecedented surveillance of the virus provides the opportunity to better understand the evolution of influenza. we examined changes in the nucleotide coding regions and the amino acid sequences of the hemagglutinin (ha), neuraminidase (na), and nucleoprotein (np) segments of the a(h1n1)pdm09 strain using publicly available data. we calculated the nucleotide and amino acid hamming distance f ...201424699432
development of high-throughput liquid chips for respiratory virus detection.diagnosis of viral respiratory tract infections clinically is often nonspecific, and a rapid, high-throughput laboratory technique which can detect major respiratory viruses is desirable.201424697109
a broadly neutralizing human monoclonal antibody directed against a novel conserved epitope on the influenza virus h3 hemagglutinin globular head.most neutralizing antibodies elicited during influenza virus infection or vaccination target immunodominant, variable epitopes on the globular head region of hemagglutinin (ha), which leads to narrow strain protection. in this report, we describe the properties of a unique anti-ha monoclonal antibody (mab), d1-8, that was derived from human b cells and exhibits potent, broad neutralizing activity across antigenically diverse influenza h3 subtype viruses. based on selection of escape variants, we ...201424696468
pestalols a-e, new alkenyl phenol and benzaldehyde derivatives from endophytic fungus pestalotiopsis sp. acbc2 isolated from the chinese mangrove plant aegiceras corniculatum.five alkenyl phenol and benzaldehyde derivatives, pestalols a-e (1-5), as well as seven known compounds (6-12), were isolated from endophytic fungus pestalotiopsis sp. acbc2 derived from the chinese mangrove plant aegiceras corniculatum. their structures were determined by spectroscopic analyses. compounds 2 and 3 showed cytotoxicity against a panel of 10 tumor cell lines. compounds 1-5, 8, 9, 11, and 12 showed inhibitory activities against influenza a virus subtype (h3n2) and swine flu (h1n1) v ...201424690916
phylogeny of spanish swine influenza viruses isolated from respiratory disease outbreaks and evolution of swine influenza virus within an endemically infected farm.in the present study, outbreaks of respiratory disease were investigated for the presence of swine influenza virus (siv). in 14 cases the circulating siv strains were isolated, fully sequenced and compared with other known sivs. the viruses causing the outbreaks belonged to the h1n1 (including human pandemic h1n1), h3n2 and h1n2 subtypes. in 11/14 cases the phylogenetic analyses indicated the occurrence of probable reassortment events. in the second part of the study, the genetic evolution of h1 ...201424685238
protective effect of fluvastatin on influenza virus infection.statins are 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors and have pleiotropic effects. it has been suggested that statins may be a potential treatment during the next influenza pandemic. in a previous study we found that a statin/caffeine combination protects balb/c mice against influenza a, subtypes haemagglutinin type 5 and neuraminidase type 1 (h5n1), h3n2 and h1n1 infection. the effect of statins alone on influenza virus infection, however, is not known. in this study, it was i ...201424676773
association between antibody titers and protection against influenza virus infection within households.previous studies have established that antibody titer measured by the hemagglutination-inhibiting (hai) assay is correlated with protection against influenza virus infection, with an hai titer of 1:40 generally associated with 50% protection.201424676208
full-genome sequences of influenza h3n2 virus strains isolated from finnish patients during the 2012-2013 epidemic season.here, we sequenced 10 influenza a(h3n2) virus genomes isolated from finnish patients diagnosed with flu-like illness during the 2012-2013 influenza season. the alignment showed a high number of amino acid substitutions (238 in total) in only 10 samples, proving that a high mutation rate exists in seasonal influenza a viruses.201424675845
protective efficacy of a high-growth reassortant swine h3n2 inactivated vaccine constructed by reverse genetic manipulation.novel reassortant h3n2 swine influenza viruses (swiv) with the matrix gene from the 2009 h1n1 pandemic virus have been isolated in many countries as well as during outbreaks in multiple states in the united states, indicating that h3n2 swiv might be a potential threat to public health. since southern china is the world's largest producer of pigs, efficient vaccines should be developed to prevent pigs from acquiring h3n2 subtype swiv infections, and thus limit the possibility of swiv infection at ...201424675833
low 2012-13 influenza vaccine effectiveness associated with mutation in the egg-adapted h3n2 vaccine strain not antigenic drift in circulating viruses.influenza vaccine effectiveness (ve) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. during the 2012-13 season, however, detailed genotypic and phenotypic characterization shows that low ve was instead related to mutations in the egg-adapted h3n2 vaccine strain rather than antigenic drift in circulating viruses.201424667168
influenza virus h1n1 activates platelets through fcγriia signaling and thrombin generation.platelets play crucial functions in hemostasis and the prevention of bleeding. during h1n1 influenza a virus infection, platelets display activation markers. the platelet activation triggers during h1n1 infection remain elusive. we observed that h1n1 induces surface receptor activation, lipid mediator synthesis, and release of microparticles from platelets. these activation processes require the presence of serum/plasma, pointing to the contribution of soluble factor(s). considering that immune ...201424665136
retrospective serology study of respiratory virus infections in captive great apes.great apes are extremely sensitive to infections with human respiratory viruses. in this study, we retrospectively analyzed sera from captive chimpanzees, gorillas and orang-utans. more than 1000 sera (403 chimpanzee, 77 gorilla, and 535 orang-utan sera) were analyzed for antibodies to the human respiratory viruses rsv (respiratory syncytial virus, hmpv (human metapneumovirus), h1n1 and h3n2 influenza a viruses, and influenza b virus. in all ape species high seroprevalences were found for rsv, h ...201424662675
one-health simulation modelling: a case study of influenza spread between human and swine populations using naadsm.the circulation of zoonotic influenza a viruses including ph1n1 2009 and h5n1 continue to present a constant threat to animal and human populations. recently, an h3n2 variant spread from pigs to humans and between humans in limited numbers. accordingly, this research investigated a range of scenarios of the transmission dynamics of ph1n1 2009 virus at the swine-human interface while accounting for different percentages of swine workers initially immune. furthermore, the feasibility of using naad ...201624661802
reserve autophagic capacity in alveolar epithelia provides a replicative niche for influenza a virus.autophagy contributes to cellular homeostasis through metabolite recycling and degradation of cytotoxic protein aggregates and damaged organelles. although recent studies have established that the requirement for basal autophagy is largely tissue specific, the importance of autophagy for alveolar epithelial cell homeostasis remains an important knowledge gap. in the present study we generated two mouse models, with > 90% or > 50% recombination at the atg5 locus in the distal respiratory epitheli ...201424661119
in vitro antiviral activity of a series of wild berry fruit extracts against representatives of picorna-, orthomyxo- and paramyxoviridae.wild berry species are known to exhibit a wide range of pharmacological activities. they have long been traditionally applied for their antiseptic, antimicrobial, cardioprotective and antioxidant properties. the aim of the present study is to reveal the potential for selective antiviral activity of total methanol extracts, as well as that of the anthocyanins and the non-anthocyanins from the following wild berries picked in bulgaria: strawberry (fragaria vesca l.) and raspberry (rubus idaeus l.) ...201424660461
cluster of influenza a cases in vaccinated population of adults in virology laboratory in glasgow in december 2012.the majority of influenza infections during the 2012/2013 influenza season in scotland have been due to influenza a h3n2. we report an outbreak of influenza a h3n2 in a vaccinated population of adults in the regional virology laboratory in glasgow. this investigation was carried out to confirm the epidemiological link between cases.201424659378
rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.live attenuated influenza vaccine viruses (laivs) can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated master donor virus (mdv) and a seasonal wild-type (wt) virus. the vaccine candidates contain hemagglutinin (ha) and neuraminidase (na) genes derived from the circulating wt viruses and the remaining six genes derived from the mdv strains. rapid, efficient selection of the viruses with 6∶2 genome compositions from the large numb ...201424647786
development of rapid immunochromatographic test for hemagglutinin antigen of h7 subtype in patients infected with novel avian influenza a (h7n9) virus.since human infection with the novel h7n9 avian influenza virus was identified in china in march 2013, the relatively high mortality rate and possibility of human-to-human transmission have highlighted the urgent need for sensitive and specific assays for diagnosis of h7n9 infection.201424647358
[development and validation of the real-time pcr assay for the identification of viral agents causing acute respiratory infections in humans].the real time pcr assay targeting influenza a and b virus, 5 subtypes of influenza a virus (seasonal h1n1, pandemic h1n1 (2009), seasonal h3n2, pathogenic for human subtypes of avian influenza h5 and h7), respiratory syncytial virus, and adenovirus was developed. the analytical sensitivity of the developed assay was 1 x 10(3) genome equivalents per ml. the diagnostic sensitivity of the method was 1 x l0(3)-10(4) viral particles per ml. experiments with human dna/cdna and viral cdna showed a mark ...201324645276
purification of vero cell derived live replication deficient influenza a and b virus by ion exchange monolith chromatography.we explored the possibilities for purification of various δns1 live, replication deficient influenza viruses on ion exchange methacrylate monoliths. influenza a δns1-h1n1, δns1-h3n2, δns1-h5n1 and δns1-influenza b viruses were propagated in vero cells and concentrated by tangential flow filtration. all four virus strains adsorbed well to cim qa and cim deae anion exchangers, with cim qa producing higher recoveries than cim deae. δns1-influenza a viruses adsorbed well also to cim so3 cation excha ...201424631091
influenza vaccine effectiveness in spain 2013/14: subtype-specific early estimates using the cyceva study.adjusted early estimates of the 2013/14 influenza vaccine effectiveness (ve) in spain for all age groups was 35% (95% ci: -9 to 62), 33% (95% ci: -33 to 67) and 28% (95% ci: -33 to 61) against any influenza virus type, a(h1n1)pdm09 and a(h3n2) viruses, respectively. for the population targeted for vaccination, the adjusted ve was 44% (95% ci: -11 to 72), 36% (95% ci: -64 to 75) and 42% (95% ci: -29 to 74), respectively. these preliminary results in spain suggest a suboptimal protective effect of ...201424626206
mucosal immunization with a candidate universal influenza vaccine reduces virus transmission in a mouse model.pandemic influenza is a major public health concern, but conventional strain-matched vaccines are unavailable early in a pandemic. candidate "universal" vaccines targeting the viral antigens nucleoprotein (np) and matrix 2 (m2), which are conserved among all influenza a virus strains and subtypes, could be manufactured in advance for use at the onset of a pandemic. these vaccines do not prevent infection but can reduce disease severity, deaths, and virus titers in the respiratory tract. we hypot ...201424623430
detection of nonhemagglutinating influenza a(h3) viruses by enzyme-linked immunosorbent assay in quantitative influenza virus culture.to assess the efficacy of novel antiviral drugs against influenza virus in clinical trials, it is necessary to quantify infectious virus titers in respiratory tract samples from patients. typically, this is achieved by inoculating virus-susceptible cells with serial dilutions of clinical specimens and detecting the production of progeny virus by hemagglutination, since influenza viruses generally have the capacity to bind and agglutinate erythrocytes of various species through their hemagglutini ...201424622097
stability of neuraminidase in inactivated influenza vaccines.influenza vaccines are effective in protecting against illness and death caused by this seasonal pathogen. antibodies that block the function of either hemagglutinin (ha) or neuraminidase (na) contribute to vaccine efficacy, however vaccine potency is based only on ha content. na protein content in vaccines varies from season to season due to differences in the relative amounts of ha and na in influenza a, h1n1 and h3n2, and influenza b viruses that are selected for each manufacturing campaign. ...201424613525
preexisting cd4+ t-cell immunity in human population to avian influenza h7n9 virus: whole proteome-wide immunoinformatics analyses.in 2013, a novel avian influenza h7n9 virus was identified in human in china. the antigenically distinct h7n9 surface glycoproteins raised concerns about lack of cross-protective neutralizing antibodies. epitope-specific preexisting t-cell immunity was one of the protective mechanisms in pandemic 2009 h1n1 even in the absence of cross-protective antibodies. hence, the assessment of preexisting cd4+ t-cell immunity to conserved epitopes shared between h7n9 and human influenza a viruses (iav) is c ...201424609014
metal enhanced fluorescence on nanoporous gold leaf-based assay platform for virus detection.in the present study, a rapid, sensitive and quantitative detection of influenza a virus targeting hemagglutinin (ha) was developed using hybrid structure of quantum dots (qds) and nanoporous gold leaf (npgl). npgl film was prepared by dealloying bimetallic film where its surface morphology and roughness were fairly controlled. anti-influenza a virus ha antibody (ab66189) was bound with npgl and amine (-nh2) terminated qds. these biofunctionalized npgl and qds formed a complex with the influenza ...201424607620
impact of 2009 pandemic influenza among vietnamese children based on a population-based prospective surveillance from 2007 to 2011.influenza virus is one of the major viral pathogens causing pediatric acute respiratory infection (ari). the spread of pandemic influenza a (a(h1n1)pdm09) in 2009 around the globe had a huge impact on global health.201424602158
the host protease tmprss2 plays a major role in in vivo replication of emerging h7n9 and seasonal influenza viruses.proteolytic cleavage of the hemagglutinin (ha) protein is essential for influenza a virus (iav) to acquire infectivity. this process is mediated by a host cell protease(s) in vivo. the type ii transmembrane serine protease tmprss2 is expressed in the respiratory tract and is capable of activating a variety of respiratory viruses, including low-pathogenic (lp) iavs possessing a single arginine residue at the cleavage site. here we show that tmprss2 plays an essential role in the proteolytic activ ...201424600012
emergence of g186d mutation in the presence of r292k mutation in an immunocompromised child infected with influenza a/h3n2 virus, treated with oseltamivir.an immunocompromised child with influenza a/h3n2 virus infection, treated with oseltamivir from day 1, had nasal swabs taken on days 1, 4, 7, and 10 of the illness. pyrosequencing showed increasing proportions of viruses with r292k (neuraminidase gene) and g186d (hemagglutinin gene) mutations, resulting in a viral load rebound by day 10.201424599981
a phospha-oseltamivir-biotin conjugate as a strong and selective adhesive for the influenza virus.we present the synthesis and application of a molecule containing both the powerful influenza neuraminidase (na) inhibitor phospha-oseltamivir and d-biotin, connected via an undecaethylene glycol spacer. it inhibits influenza virus neuraminidase (from the h3n2 x31 virus) in the same range as oseltamivir, with a slow off-rate, and produces a stable na-coated surface when loaded onto streptavidin-coated biosensors. purified x31 virus binds to these loaded biosensors with an apparent dissociation c ...201424594352
supplementation of influenza split vaccines with conserved m2 ectodomains overcomes strain specificity and provides long-term cross protection.current influenza vaccines do not provide good protection against antigenically different influenza a viruses. as an approach to overcome strain specificity of protection, this study demonstrates significantly improved long-term cross protection by supplementing split vaccines with a conserved molecular target, a repeat of the influenza m2 ectodomain (m2e) expressed on virus-like particles (m2e5x vlps) in a membrane-anchored form. intramuscular immunization with h1n1 split vaccine (a/california/ ...201424590045
1,2,3-triazole-containing derivatives of rupestonic acid: click-chemical synthesis and antiviral activities against influenza viruses.two series of rupestonic acid derivatives, (1-substituted-1h-1,2,3-triazol-4-yl)methyl 2-((5r,8s,8as)-3,8-dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octahydroazulen-5-yl)acrylate and n-(1-substituted-1h-1,2,3-triazol-4-yl)methyl 2-((5r,8s,8as)-3,8-dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octahydroazulen-5-yl)acrylamide were easily and efficiently synthesized via click chemistry. these compounds were tested for their in vitro activities against various strains of influenza a virus (h1n1, oseltamivir resistant h1n1, ...201424583605
oseltamivir-zanamivir combination therapy is not superior to zanamivir monotherapy in mice infected with influenza a(h3n2) and a(h1n1)pdm09 viruses.the efficacy of oseltamivir-zanamivir combination therapy compared to that of monotherapy was evaluated in mice infected with influenza a(h3n2) or a(h1n1)pdm09 viruses. for a(h3n2) virus, zanamivir monotherapy and oseltamivir-zanamivir combination showed significant reduction of mean weight loss compared to oseltamivir. zanamivir monotherapy also conferred decreased mortality, weight loss and lung viral titers (lvt) compared to oseltamivir for a(h1n1)pdm09 wild-type virus. intermediate benefits ...201424583158
(19)f nmr reveals multiple conformations at the dimer interface of the nonstructural protein 1 effector domain from influenza a virus.nonstructural protein 1 of influenza a virus (ns1a) is a conserved virulence factor comprised of an n-terminal double-stranded rna (dsrna)-binding domain and a multifunctional c-terminal effector domain (ed), each of which can independently form symmetric homodimers. here we apply (19)f nmr to ns1a from influenza a/udorn/307/1972 virus (h3n2) labeled with 5-fluorotryptophan, and we demonstrate that the (19)f signal of trp187 is a sensitive, direct monitor of the ed helix:helix dimer interface. ( ...201424582435
synthesis and anti-influenza activities of novel baicalein analogs.a series of novel flavones derivatives were synthesized based on modification of the active ingredients of a traditional chinese medicine scutellaria baicalensis georgi and screened for anti-influenza activity. the synthetic baicalein (flavone) analogs, especially with the b-rings substituted with bromine atoms, were much more potent than oseltamivir or ribavirin against h1n1 tamiflu-resistant (h1n1 tr) virus and usually with more favorable selectivity. the most promising were 5b, 5c, 6b and 6c, ...201424572377
a predictive fitness model for influenza.the seasonal human influenza a/h3n2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. adaptive mutations respond to human immune challenge and occur primarily in antigenic epitopes, the antibody-binding domains of the viral surface protein haemagglutinin. here we develop a fitness model for haemagglutinin that predicts the evolution of the viral population from one year to the next. two factors are shown to determ ...201424572367
evaluation of screening assays for the detection of influenza a virus serum antibodies in swine.increased surveillance of influenza a virus (iav) infections in human and swine populations is mandated by public health and animal health concerns. antibody assays have proven useful in previous surveillance programmes because antibodies provide a record of prior exposure and the technology is inexpensive. the objective of this research was to compare the performance of influenza serum antibody assays using samples collected from pigs (vaccinated or unvaccinated) inoculated with either a/swine/ ...201624571447
viral aetiology influenza like illnesses in santa cruz, bolivia (2010-2012).acute respiratory infections represent a serious public health issue worldwide but virological aetiologies of influenza like illnesses (ilis) remain largely unknown in developing countries. this study represents the first attempt to characterise viral aetiologies of ilis in bolivia.201424564892
intranasal vaccination with a replication-deficient influenza virus induces heterosubtypic neutralising mucosal iga antibodies in humans.we investigated the cross-neutralising potential of serum and nasal wash samples from volunteers who were intranasally immunised once with a monovalent replication-deficient delns1-h1n1 influenza virus vaccine (7.7log10tcid50/volunteer). eight out of twelve (8/12) vaccinees responded to vaccination with a significant increase of antibody levels in serum igg elisa, mucosal iga elisa, mna or hai. four responders showed delns1-specific elisa iga increases and revealed excellent homosubtypic neutral ...201424560674
in vitro neuraminidase inhibitory activity of four neuraminidase inhibitors against influenza virus isolates in the 2011-2012 season in japan.the neuraminidase inhibitors oseltamivir phosphate (tamiflu®), zanamivir (relenza®), laninamivir octanoate (inavir®), and peramivir (rapiacta®) have been available for the treatment of influenza in japan since 2010. to assess the extent of viral resistance, we measured the 50% inhibitory concentration (ic₅₀) of each drug for influenza virus isolates from the 2011-2012 influenza season. specimens were obtained from patients prior to treatment. viral isolation was done using madine-darby canine ki ...201424560563
live attenuated influenza vaccine enhances colonization of streptococcus pneumoniae and staphylococcus aureus in mice.community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. what has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (laivs). using a mouse-adapted laiv against influenza a (h3n2) virus carrying the same mutations as the human flumist vaccine, we find that laiv vacc ...201424549845
h3n2 virus as causative agent of ards requiring extracorporeal membrane oxygenation support.pandemic influenza virus a(h1n1) 2009 was associated with a higher risk of viral pneumonia in comparison with seasonal influenza viruses. the influenza season 2011-2012 was characterized by the prevalent circulation of influenza a(h3n2) viruses. whereas most h3n2 patients experienced mild, self-limited influenza-like illness, some patients were at increased risk for influenza complications because of age or underlying medical conditions. cases presented were patients admitted to the intensive ca ...201424527039
phylogenetic analysis of a swine influenza a(h3n2) virus isolated in korea in 2012.influenza a virus (iav) can infect avian and mammalian species, including humans. the genome nature of iavs may contribute to viral adaptation in different animal hosts, resulting in gene reassortment and the reproduction of variants with optimal fitness. as seen again in the 2009 swine-origin influenza a h1n1 pandemic, pigs are known to be susceptible to swine, avian, and human iavs and can serve as a 'mixing vessel' for the generation of novel iav variants. to this end, the emergence of swine ...201424523938
tmprss2 is a host factor that is essential for pneumotropism and pathogenicity of h7n9 influenza a virus in mice.cleavage of the hemagglutinin (ha) by host proteases is essential for the infectivity of influenza viruses. here, we analyzed the role of the serine protease tmprss2, which activates ha in the human respiratory tract, in pathogenesis in a mouse model. replication of the human h7n9 isolate a/anhui/1/13 and of human h1n1 and h3n2 viruses was compared in tmprss2 knockout (tmprss2(-/-)) and wild-type (wt) mice. knockout of tmprss2 expression inhibited h7n9 influenza virus replication in explants of ...201424522916
substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza a h3n2 viruses in u.s. swine.swine influenza a virus is an endemic and economically important pathogen in pigs, with the potential to infect other host species. the hemagglutinin (ha) protein is the primary target of protective immune responses and the major component in swine influenza a vaccines. however, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. characterizing the cross-reactivity between strains in pigs and seasonal influenza virus strains in huma ...201424522915
prospective surveillance and molecular characterization of seasonal influenza in a university cohort in singapore.southeast asia is believed to be a potential locus for the emergence of novel influenza strains, and therefore accurate sentinel surveillance in the region is critical. limited information exists on sentinel surveillance of influenza-like illness (ili) in young adults in singapore in a university campus setting. the objective of the present study was to determine the proportion of ili caused by influenza a and b viruses in a university cohort in singapore.201424520371
influenza a virus infections in marine mammals and terrestrial carnivores.influenza a viruses (iav), members of the orthomyxoviridae, cover a wide host spectrum comprising a plethora of avian and, in comparison, a few mammalian species. the viral reservoir and gene pool are kept in metapopulations of aquatic wild birds. the mammalian-adapted iavs originally arose by transspecies transmission from avian sources. in swine, horse and man, species-adapted iav lineages circulate independently of the avian reservoir and cause predominantly respiratory disease of highly vari ...201424511825
integrating influenza antigenic dynamics with molecular evolution.influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (hi) assay. here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phy ...201424497547
transcriptomic characterization of the novel avian-origin influenza a (h7n9) virus: specific host response and responses intermediate between avian (h5n1 and h7n7) and human (h3n2) viruses and implications for treatment options.a novel avian-origin h7n9 influenza a virus (iav) emerged in china in 2013, causing mild to lethal human respiratory infections. h7n9 originated with multiple reassortment events between avian viruses and carries genetic markers of human adaptation. determining whether h7n9 induces a host response closer to that with human or avian iav is important in order to better characterize this emerging virus. here we compared the human lung epithelial cell response to infection with a/anhui/01/13 (h7n9) ...201424496798
differences in antibody responses between trivalent inactivated influenza vaccine and live attenuated influenza vaccine correlate with the kinetics and magnitude of interferon signaling in children.live attenuated influenza vaccine (laiv) and trivalent inactivated influenza vaccine (tiv) are effective for prevention of influenza virus infection in children, but the mechanisms associated with protection are not well defined.201424495909
dietary enterococcus faecium ncimb 10415 and zinc oxide stimulate immune reactions to trivalent influenza vaccination in pigs but do not affect virological response upon challenge infection.swine influenza viruses (siv) regularly cause significant disease in pigs worldwide. since there is no causative treatment of siv, we tested if probiotic enterococcus (e.) faecium ncimb 10415 or zinc (zn) oxide as feed supplements provide beneficial effects upon siv infection in piglets. seventy-two weaned piglets were fed three different diets containing either e. faecium or different levels of zn (2500 ppm, zn(high); 50 ppm, zn(low)). half of the piglets were vaccinated intramuscularly (vac) t ...201424489827
a new class of synthetic anti-lipopolysaccharide peptides inhibits influenza a virus replication by blocking cellular attachment.influenza a viruses are a continuous threat to human health as illustrated by the 2009 h1n1 pandemic. since circulating influenza virus strains become increasingly resistant against currently available drugs, the development of novel antivirals is urgently needed. here, we have evaluated a recently described new class of broad-spectrum antiviral peptides (synthetic anti-lipopolysaccharide peptides; salps) for their potential to inhibit influenza virus replication in vitro and in vivo. we found t ...201424486207
the duration of fever and other symptoms after the initiation of laninamivir octanoate hydrate in the japanese 2011-2012 influenza season.laninamivir octanoate hydrate (laninamivir) is a long-acting, single inhalation neuraminidase inhibitor that was approved in japan in 2010 for the treatment of influenza a and b virus infection. we investigated the duration of fever and other symptoms after the initiation of laninamivir in the japanese 2011-2012 influenza season. virus isolation was done and the 50% inhibitory concentration (ic₅₀) was measured for the virus isolates at days 1 and 5. for 211 patients (a(h3n2): 190, b: 21), the me ...201424486167
intranasal vaccination promotes detrimental th17-mediated immunity against influenza infection.influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. we evaluated the efficacy of a synthetic toll-like receptor 4 agonist crx-601 as an adjuvant for enhancing vaccine-induced protection against influenza infectio ...201424465206
predictability of antigenic evolution for h3n2 human influenza a virus.influenza a virus continues to pose a threat to public health. since this virus can evolve escape mutants rapidly, it is desirable to predict the antigenic evolution for developing effective vaccines. although empirical methods have been proposed and reported to predict the antigenic evolution more or less accurately, they did not provide much insight into the effects of unobserved mutations and the mechanisms of antigenic evolution. here a theoretical method was introduced to predict the antige ...201324463525
genetic characterization of influenza a viruses circulating in pigs and isolated in north-east spain during the period 2006-2007.swine influenza virus is one of the most important pathogens involved in the swine respiratory disease complex. recent serological surveys showed a high prevalence of swine influenza strains belonging to the h1n1, h1n2 and h3n2 subtypes circulating in pigs in spain. however, little is known about their genome sequence. five swine influenza strains were isolated from some unrelated outbreaks occurred during 2006-2007, and their complete genome sequences were determined. phylogenetic analysis reve ...201424461956
epidemiological analysis of influenza a infection in cambodian pigs and recommendations for surveillance strategies.this study analysed the available data of seroprevalence to human influenza viruses in pigs in cambodia using generalized linear mixed models in order to improve understanding of factors underlying the spread of human influenza viruses in cambodian pigs. the associations between seroprevalence against seasonal h1n1 influenza virus in pigs and the population density of humans and pigs were not significant. however, a positive association between anti-h3 antibodies in pigs and the human population ...201524460959
antiviral susceptibility of variant influenza a(h3n2)v viruses isolated in the united states from 2011 to 2013.since 2011, outbreaks caused by influenza a(h3n2) variant [a(h3n2)v] viruses have become a public health concern in the united states. the a(h3n2)v viruses share the a(h1n1)pdm09 m gene containing the marker of m2 blocker resistance, s31n, but do not contain any known molecular markers associated with resistance to neuraminidase (na) inhibitors (nais). using a fluorescent na inhibition (ni) assay, the susceptibilities of recovered a(h3n2)v viruses (n=168) to fda-approved (oseltamivir and zanamiv ...201424449767
evidence for a crucial role of a host non-coding rna in influenza a virus replication.a growing body of evidence suggests the non-protein coding human genome is of vital importance for human cell function. besides small rnas, the diverse class of long non-coding rnas (lncrnas) recently came into focus. however, their relevance for infection, a major evolutionary driving force, remains elusive. using two commercially available microarray systems, namely ncode™ and sureprint™ g3, we identified differential expression of 42 ncrnas during influenza a virus (iav) infection in human lu ...201324440876
structural insights into the membrane fusion mechanism mediated by influenza virus hemagglutinin.membrane fusion is involved in many fundamental cellular processes and entry of enveloped viruses into host cells. influenza type a virus ha has long served as a paradigm for mechanistic studies of protein-mediated membrane fusion via large-scale structural rearrangements induced by acidic ph. here we report the newly determined crystal structure of influenza b virus ha2 in the postfusion state. together with a large number of previously determined prefusion structures of influenza a and b virus ...201424433110
repetitive fulminant influenza myocarditis requiring the use of circulatory assist devices.a 52-year-old man was admitted to our hospital due to shortness of breath that developed one week after the diagnosis of influenza infection. he had a past history of myocarditis associated with influenza b infection 16 years before the current admission. the patient's left ventricular function showed diffuse hypokinesis with a left ventricular ejection fraction of 28%. due to the progression of heart failure, the infusion of catecholamines and insertion of an intra-aortic balloon pump were requ ...201424429449
novel oral anti-influenza prodrug candidate av5075s.development of a novel drug candidate with improved activity against influenza virus neuraminidase (na) compared with currently available therapeutics.201424428978
serum 25-hydroxyvitamin d level and influenza vaccine immunogenicity in children and adolescents.vaccination is an important strategy in the prevention of influenza, but immunologic response to vaccination can vary widely. recent studies have shown an association between serum 25-hydroxyvitamin d (25[oh]d) levels and immune function. the purpose of this study was to determine if serum 25(oh)d level correlates with influenza vaccine immunogenicity in children and adolescents.201424427274
mechanism of a decrease in potency for the recombinant influenza a virus hemagglutinin h3 antigen during storage.the recombinant hemagglutinin (rha)-based influenza vaccine flublok® has recently been approved in the united states as an alternative to the traditional egg-derived flu vaccines. flublok is a purified vaccine with a hemagglutinin content that is threefold higher than standard inactivated influenza vaccines. when rha derived from an h3n2 influenza virus was expressed, purified, and stored for 1 month, a rapid loss of in vitro potency (∼50%) was observed as measured by the single radial immunodif ...201424425059
synthesis, structure and inhibitory activity of a stereoisomer of oseltamivir carboxylate.a stereodivergent plan is presented leading to all eight stereoisomers of oseltamivir carboxylate (oc). key chemical manoeuvers are (1) a three-component vinylogous mukaiyama-mannich reaction, which sets the whole carbon skeleton and heteroatom substituents, and (2) an intramolecular, silylative mukaiyama aldol reaction, which creates the targeted carbocycle. the viability of the plan was demonstrated by the first total synthesis of 4-epi-oseltamivir carboxylate (6), accessed in 15 steps from gl ...201424425043
evaluation of heterosubtypic cross-protection against highly pathogenic h5n1 by active infection with human seasonal influenza a virus or trivalent inactivated vaccine immunization in ferret models.the threat of highly pathogenic avian influenza (hpai) h5n1 viruses to cause the next pandemic remains a major concern. here, we evaluated the cross-protection induced by natural infection of human seasonal influenza strains or immunization with trivalent inactivated influenza vaccine (tiv) against hpai h5n1 (a/vietnam/1203/2004) virus in ferrets. groups were treated with pbs (group a), infected with h1n1 (group b) or h3n2 (group c) virus, or immunized with tiv (group d). twelve weeks after the ...201424421115
intrasubtype reassortments cause adaptive amino acid replacements in h3n2 influenza genes.reassortments and point mutations are two major contributors to diversity of influenza a virus; however, the link between these two processes is unclear. it has been suggested that reassortments provoke a temporary increase in the rate of amino acid changes as the viral proteins adapt to new genetic environment, but this phenomenon has not been studied systematically. here, we use a phylogenetic approach to infer the reassortment events between the 8 segments of influenza a h3n2 virus since its ...201424415946
establishment of serological herd profiles for zoonoses and production diseases in pigs by "meat juice multi-serology".the most important pork-borne zoonotic diseases in humans such as salmonelloses and yersinioses cause only latent infections in pigs. thus, the infection of pigs does not result in apparent or palpable alterations in the pig carcasses. this is the major reason, why the traditional meat inspection with adspection, palpation and incision is not able to control the food safety risks of today. the objective of this paper is to evaluate a set of serological tests, which provides a classification of p ...201424411983
immunogenicity of a 2009 pandemic influenza virus a h1n1 vaccine, administered simultaneously with the seasonal influenza vaccine, in children receiving chemotherapy.no examination of simultaneous vaccination against pandemic h1n1 and the seasonal influenza virus strains, in children with cancer receiving chemotherapy, are yet published. we investigated the immunogenicity of a whole-virion, inactivated, adjuvanted pandemic h1n1, and seasonal influenza vaccines administered simultaneously to children with cancer undergoing chemotherapy.201424395342
identification of adaptive mutations in the influenza a virus non-structural 1 gene that increase cytoplasmic localization and differentially regulate host gene expression.the ns1 protein of influenza a virus (iav) is a multifunctional virulence factor. we have previously characterized gain-of-function mutations in the ns1 protein arising from the experimental adaptation of the human isolate a/hong kong/1/1968(h3n2) (hk) to the mouse. the majority of these mouse adapted ns1 mutations were demonstrated to increase virulence, viral fitness, and interferon antagonism, but differ in binding to the post-transcriptional processing factor cleavage and polyadenylation spe ...201324391972
recombinant porcine surfactant protein d inhibits influenza a virus replication ex vivo.influenza is a major burden to public health. due to high mutation rates and selection pressure, mutant viruses emerge which are resistant to currently used antiviral drugs. therefore, there is a need for the development of novel classes of antiviral drugs that suffer less from the emergence of resistant viruses. antiviral drugs based on collectin-like surfactant protein d (sp-d) may fulfil these requirements. especially porcine sp-d displays strong antiviral activity to influenza a viruses. in ...201424389095
cyclic dipeptides from lactic acid bacteria inhibit proliferation of the influenza a virus.we isolated lactobacillus plantarum lbp-k10 from the traditional korean fermented food kimchi. when organic acids were removed, the culture filtrate of this isolate showed high antiviral activity (measured using a plaque-forming assay) against the influenza a (h3n2) virus. two fractions that were active against influenza a virus were purified from the culture filtrate using a c18 column with high-performance liquid chromatography. these active fractions were crystallized and identified to be the ...201324385362
inferring the antigenic epitopes for highly pathogenic avian influenza h5n1 viruses.the evasion of influenza virus from host immune surveillance is mainly mediated through its surface protein hemagglutinin (ha), the main component of influenza vaccine. thus, identification of influenza virus antigenic epitopes on ha can not only help us understand the molecular mechanisms of viral immune escape but also facilitate vaccine strain selection. despite previous efforts, there is a lack of systematic definition of the antigenic epitopes for the highly pathogenic avian influenza (hpai ...201424380681
a historical perspective of influenza a(h1n2) virus.the emergence and transition to pandemic status of the influenza a(h1n1)a(h1n1)pdm09) virus in 2009 illustrated the potential for previously circulating human viruses to re-emerge in humans and cause a pandemic after decades of circulating among animals. within a short time of the initial emergence of a(h1n1)pdm09 virus, novel reassortants were isolated from swine. in late 2011, a variant (v) h3n2 subtype was isolated from humans, and by 2012, the number of persons infected began to increase wit ...201424377419
severity of the two post-pandemic influenza seasons 2010-11 and 2011-12 in northern greece.since the pandemic in 2009, the two following post pandemic influenza seasons have been associated with increased morbidity and mortality rates in northern greece. the scope of this short report is to provide relevant epidemiological information, an evaluation of the efficacy of the seasonal vaccine and antiviral drugs. molecular analysis revealed the close match of a(h1n1) 2009 pandemic and post-pandemic 2010-11 viruses with the vaccine virus. however, a proportion of the influenza a(h3n2) and ...201324376321
bifunctional thiosialosides inhibit influenza virus.we have synthesized a panel of bivalent s-sialoside analogues, with modifications at the 4 position, as inhibitors of influenza virus. these first generation compounds show ic50 values ranging from low micromolar to high nanomolar in enzyme inhibition and plaque reduction assays with two intact viruses, influenza h1n1 (a/california/07/2009) and h3n2 (a/hongkong/8/68).201424374271
genetic and antigenic typing of seasonal influenza virus breakthrough cases from a 2008-2009 vaccine efficacy trial.estimations of the effectiveness of vaccines against seasonal influenza virus are guided by comparisons of the antigenicities between influenza virus isolates from clinical breakthrough cases with strains included in a vaccine. this study examined whether the prediction of antigenicity using a sequence analysis of the hemagglutinin (ha) gene-encoded ha1 domain is a simpler alternative to using the conventional hemagglutination inhibition (hi) assay, which requires influenza virus culturing. spec ...201424371255
h1n1, but not h3n2, influenza a virus infection protects ferrets from h5n1 encephalitis.seasonal influenza causes substantial morbidity and mortality because of efficient human-to-human spread. rarely, zoonotic strains of influenza virus spread to humans, where they have the potential to mediate new pandemics with high mortality. we studied systemic viral spread after intranasal infection with highly pathogenic avian influenza virus (h5n1 [a/viet nam/1203/2004]) in ferrets with or without prior pandemic h1n1pdm09 (a/mexico/4108/2009) or h3n2 (a/victoria/361/2011) infection. after i ...201324371072
genomewide analysis of reassortment and evolution of human influenza a(h3n2) viruses circulating between 1968 and 2011.influenza a(h3n2) viruses became widespread in humans during the 1968 h3n2 virus pandemic and have been a major cause of influenza epidemics ever since. these viruses evolve continuously by reassortment and genomic evolution. antigenic drift is the cause for the need to update influenza vaccines frequently. using two data sets that span the entire period of circulation of human influenza a(h3n2) viruses, it was shown that influenza a(h3n2) virus evolution can be mapped to 13 antigenic clusters. ...201424371052
influenza associated mortality in southern china, 2010-2012.influenza caused substantial morbidity and mortality worldwide. the mortality burden caused by influenza has been under evaluation; however, data assessing this burden have been relatively sparse in tropical or subtropical regions. we estimated influenza-associated mortality in guangzhou, china and assessed the excess mortality due to different influenza virus subtypes.201424370709
influenza a virus infections in swine: pathogenesis and diagnosis.influenza has been recognized as a respiratory disease in swine since its first appearance concurrent with the 1918 "spanish flu" human pandemic. all influenza viruses of significance in swine are type a, subtype h1n1, h1n2, or h3n2 viruses. influenza viruses infect epithelial cells lining the surface of the respiratory tract, inducing prominent necrotizing bronchitis and bronchiolitis and variable interstitial pneumonia. cell death is due to direct virus infection and to insult directed by leuk ...201424363301
phylodynamics of the emergence of influenza viruses after cross-species transmission.human populations are constantly exposed to emerging pathogens such as influenza a viruses that result from cross-species transmissions. generally these sporadic events are evolutionary dead-ends, but occasionally, viruses establish themselves in a new host that offers a novel genomic context to which the virus must adjust to avoid attenuation. however, the dynamics of this process are unknown. here we present a novel method to characterize the time it takes to g+c composition at third codon pos ...201324358190
tmprss2 is essential for influenza h1n1 virus pathogenesis in mice.annual influenza epidemics and occasional pandemics pose a severe threat to human health. host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. the cleavage activation of the influenza virus hemagglutinin (ha) by host cell proteases is essential for viral infectivity. however, it is unknown which proteases activate influenza viruses in mammals. several candidates have been identified in cell culture studie ...201324348248
predicting the emergence of h3n2 influenza viruses reveals contrasted modes of evolution of ha and na antigens.vaccine design for rapidly changing viruses is based on empirical surveillance of strains circulating in a given season to assess those that will most likely spread during the next season. the choice of which strains to include in the vaccine is critical, as an erroneous decision can lead to a nonimmunized human population that will then be at risk in the face of an epidemic or, worse, a pandemic. here, we present the first steps toward a very general phylogenetic approach to predict the emergen ...201424343641
protective efficacy in mice of monovalent and trivalent live attenuated influenza vaccines in the background of cold-adapted a/x-31 and b/lee/40 donor strains.influenza virus continues to take a heavy toll on human health and vaccination remains the mainstay of efforts to reduce the clinical impact imposed by viral infections. proven successful for establishing live attenuated vaccine donor strains, cold-adapted live attenuated influenza vaccines (caivs) have become an attractive modality for controlling the virus infection. previously, we developed the cold-adapted strains a/x-31 and b/lee/40 as novel donor strains of caivs against influenza a and b ...201424342248
a common solution to group 2 influenza virus neutralization.the discovery and characterization of broadly neutralizing antibodies (bnabs) against influenza viruses have raised hopes for the development of monoclonal antibody (mab)-based immunotherapy and the design of universal influenza vaccines. only one human bnab (cr8020) specifically recognizing group 2 influenza a viruses has been previously characterized that binds to a highly conserved epitope at the base of the hemagglutinin (ha) stem and has neutralizing activity against h3, h7, and h10 viruses ...201424335589
a patient who survived primary seasonal influenza viral pneumonia: histologic findings obtained via bronchoscopy.the histological findings and clinical course of primary seasonal influenza viral pneumonia have not been fully elucidated. we herein report the case of a 65-year-old man with primary seasonal influenza viral pneumonia. the patient presented with fever, myalgia, general fatigue and dyspnea of seven days duration. chest computed tomography showed bilateral ground-glass opacity and consolidation. a rapid influenza virus antigen test was positive for influenza a virus. we diagnosed him as having co ...201324334588
comparative analysis of micrornas from the lungs and trachea of dogs (canis familiaris) infected with canine influenza virus.micrornas (mirnas) are a class of endogenous non-coding small rnas of 18-22-nucleotides in length that regulate gene expression at the post-transcriptional level. the objective of this study was to examine the differences in the mirna expression profiles of the lungs and trachea of beagle dogs infected with canine influenza virus (civ). total rna was isolated from lung and trachea tissues of beagle dogs infected and non-infected with h3n2 civ at 4 dpi. a total of 41,512,315 and 39,107,475 reads ...201424333372
influenza a(h7n9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or transmissibility.without baseline human immunity to the emergent avian influenza a(h7n9) virus, neuraminidase inhibitors are vital for controlling viral replication in severe infections. an amino acid change in the viral neuraminidase associated with drug resistance, na-r292k (n2 numbering), has been found in some h7n9 clinical isolates. here we assess the impact of the na-r292k substitution on antiviral sensitivity and viral replication, pathogenicity and transmissibility of h7n9 viruses. our data indicate that ...201324326875
egg- or cell culture-derived hemagglutinin mutations impair virus stability and antigen content of inactivated influenza vaccines.egg-derived viruses are the only available seed material for influenza vaccine production. vaccine manufacturing is done in embryonated chicken eggs, mdck or vero cells. in order to contribute to efficient production of influenza vaccines, we investigate whether the quality of inactivated vaccines is influenced by the propagation substrate. we demonstrate that h3n2 egg-derived seed viruses (a/brisbane/10/07, ivr147, and a/uruguay/716/07) triggered the hemagglutinin (ha) conformational change und ...201424323790
[selection pressure analysis of h3n2 influenza virus from china between 1992 and 2012].in order to investigate the relationship between selection pressure and the prevalence of antigenic clusters, we sequenced and analyzed the h3n2 influenza virus from china between 1992 and 2012.201324319949
genetic characterization of seasonal influenza a (h3n2) viruses in ontario during 2010-2011 influenza season: high prevalence of mutations at antigenic sites.the direct effect of antigenic site mutations in influenza viruses on antigenic drift and vaccine effectiveness is poorly understood.201424313991
a single amino acid substitution in the hemagglutinin of h3n2 subtype influenza a viruses is associated with resistance to the long pentraxin ptx3 and enhanced virulence in mice.the long pentraxin, pentraxin 3 (ptx3), can play beneficial or detrimental roles during infection and disease by modulating various aspects of the immune system. there is growing evidence to suggest that ptx3 can mediate antiviral activity in vitro and in vivo. previous studies demonstrated that ptx3 and the short pentraxin serum amyloid p express sialic acids that are recognized by the hemagglutinin (ha) glycoprotein of certain influenza a viruses (iav), resulting in virus neutralization and an ...201424307735
comparative analysis of receptor-binding specificity and pathogenicity in natural reassortant and non-reassortant h3n2 swine influenza virus.genetic reassortment between human and avian influenza viruses can create pandemic viruses. influenza surveillance of pigs in jilin province, in china during 2007-2008 revealed that there were two distinguishable genotypes: a human-like h3n2 genotype and a double-reassortant genotype derived from the human h3n2 and avian h5 viruses. in this study, viral infection potential, replication kinetics, and pathogenicity were compared. the solid-phase binding assay demonstrated that both viruses promine ...201424305615
drug susceptibility surveillance of influenza viruses circulating in the united states in 2011-2012: application of the who antiviral working group criteria.assessing susceptibility of influenza viruses to neuraminidase (na) inhibitors (nais) is primarily done in na inhibition (ni) assays, supplemented by na sequence analysis. however, two factors present challenges for ni assay data interpretation: lack of established ic50 values indicative of clinically relevant resistance and insufficient harmonization of ni testing methodologies among surveillance laboratories. in 2012, the who working group on influenza antiviral susceptibility (who-avwg) devel ...201424299049
avian-origin h3n2 canine influenza virus circulating in farmed dogs in guangdong, china.since 2006, more and more cases of the infectious h3n2 canine influenza virus (civ) in pet dogs have been reported in southern china. however, little is known about the prevalence situation of h3n2 civ infections in farmed dogs in china. this is the first systematic epidemiological surveillance of civ in different dog populations in southern china. two virus strains a/canine/guangdong/1/2011(h3n2) and a/canine/guangdong/5/2011(h3n2) were isolated from canine nasal swabs collected at one dog farm ...201324298574
the use of antiviral drugs for influenza: guidance for practitioners 2012/2013.the present article addresses the use of antiviral drugs in the management of seasonal influenza illness for the 2012/2013 season. it updates the previous document published in 2011 (1). noteworthy guidance updates since 2011 include the following: seasonal influenza in 2012/2013 is predicted to be caused by two human influenza a and one influenza b strain, all of which are anticipated to remain generally susceptible to oseltamivir.the predicted strains are a/california/7/2009 (h1n1) pdm09-like, ...201224294283
different evolutionary trends of swine h1n2 influenza viruses in italy compared to european viruses.european h1n2 swine influenza viruses (eu h1n2sivs) arose from multiple reassortment events among human h1n1, human h3n2, and avian influenza viruses. we investigated the evolutionary dynamics of 53 italian h1n2 strains by comparing them with eu h1n2 sivs. hemagglutinin (ha) phylogeny revealed italian strains fell into four groups: group a and b (41 strains) had a human h1 similar to eu h1n2sivs, which probably originated in 1986. however group b (38 strains) formed a subgroup that had a two-ami ...201324289094
influenza vaccine response in adults exposed to perfluorooctanoate and perfluorooctanesulfonate.supported by several epidemiological studies and a large number of animal studies, certain polyfluorinated alkyl acids are believed to be immunotoxic, affecting particularly humoral immunity. our aim was to investigate the relationship between the antibody response following vaccination with an inactivated trivalent influenza vaccine and circulating levels of perfluorooctanoate (pfoa) and perfluorooctanesulfonate (pfos). the study population consisted of 411 adults living in the mid-ohio region ...201424284791
homosecoiridoid alkaloids with amino acid units from the flower buds of lonicera japonica.nine new homosecoiridoid alkaloids, named lonijaposides o-w (1-9), along with 19 known compounds, were isolated from an aqueous extract of the flower buds of lonicera japonica. their structures and absolute configurations were determined by spectroscopic data analysis and chemical methods. lonijaposides o-w have structural features that involve amino acid units sharing the n atom with a pyridinium (1-5) or nicotinic acid (6-9) moiety. the absolute configurations of the amino acid units were dete ...201324279769
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