A radiometric method for the assay of ganglioside sialidase in cultured human fibroblasts was set up. As substrate, highly radioactive (1.28 Ci/mmol) ganglioside GD1a isotopically tritium-labeled at carbon C-3 of the long chain base was employed; the liberated, and TLC separated [3H]GM1 was determined by computer-assisted radiochromatoscanning. Under experimental conditions that provided a low and quite acceptable (4-5%) coefficient of variation, the detection limit of the method was 0.1 nmol of liberated GM1, using as low as 10 μg of fibroblast homogenate as protein. The detection limit could be lowered to 0.02-0.03 nmol, adopting conditions that, however, carried a higher analytical error (coefficient of variation over 10%). The content of ganglioside sialidase in human fibroblasts cultured in 75-cm2 plastic flasks was 5.8 ∓ 2.5 (SD) nmol liberated GM1 h-1 mg protein-1. Subfractionation studies performed on fibroblast homogenate showed that the ganglioside sialidase was mainly associated ...

Lysosomal Storage Disorders are a class of inherited metabolic conditions that result from alterations in the function of lysosomal enzymes. One example is GM1 Gangliosidosis (GM1), a disorder in which the activity of β-galactosidase is deficient resulting in neurodegeneration and early death. The enzyme, β-gal, is a member of the Lysosomal Multienzyme Complex (LMC), which transports proteins to the lysosome and enables various functions. LMC members include β-gal, α-neuraminidase and the Protective Protein Cathepsin A (PPCA). In a unique ovine model of GM1, there is a primary deficiency in the activity of β- galactosidase and a secondary deficiency in α-neuraminidase activity. The cause of the secondary deficiency in α-neuraminidase activity, which is not seen in any other animal model of GM1, is currently unknown. The α-neuraminidase protein is coded for by the NEU1 gene and is, a glycohydrolitic enzyme that is active in the lysosome. The secondary deficiency of α- neuraminidase seen in our

Our study provides validated virus inactivation protocols that allow implementation of phenotypic NAI susceptibility testing, HI assessment (for serology as well antigenic characterization of viruses), and T-cell response characterization using avian, swine, and human influenza viruses under BSL-2 containment conditions. Using pandemic influenza A(H1N1)v virus strains, we illustrate the ease of carrying out Triton X-100 and formalin virus inactivation protocols prior to the assessment of A(H1N1)v virus susceptibility to antivirals and the characterization of B- and T-cell responses, respectively, outside the BSL-3 high-containment facility. These inactivation protocols facilitate the diagnostic examination of pandemic influenza viruses by applying standard laboratory conditions at BSL-2.. Considering results from documented studies and taking ease of use under BSL-3 conditions into account, therefore excluding, e.g., irradiation protocols, we evaluated human A(H3N2) and avian A(H7N3) virus ...

Our study provides validated virus inactivation protocols that allow implementation of phenotypic NAI susceptibility testing, HI assessment (for serology as well antigenic characterization of viruses), and T-cell response characterization using avian, swine, and human influenza viruses under BSL-2 containment conditions. Using pandemic influenza A(H1N1)v virus strains, we illustrate the ease of carrying out Triton X-100 and formalin virus inactivation protocols prior to the assessment of A(H1N1)v virus susceptibility to antivirals and the characterization of B- and T-cell responses, respectively, outside the BSL-3 high-containment facility. These inactivation protocols facilitate the diagnostic examination of pandemic influenza viruses by applying standard laboratory conditions at BSL-2.. Considering results from documented studies and taking ease of use under BSL-3 conditions into account, therefore excluding, e.g., irradiation protocols, we evaluated human A(H3N2) and avian A(H7N3) virus ...

Gangliosides are sialic acid-containing glycosphingolipids mainly expressed at the outer leaflet of the plasma membrane. Sialidase NEU3 is a key enzyme in the catabolism of gangliosides with its up-regulation having been observed in human cancer cells. In the case of CME (clathrin-mediated endocytosis), although this has been widely studied, the role of NEU3 and gangliosides in this cellular process has not yet been established. In the present study, we found an increased internalization of Tf (transferrin), the archetypical cargo for CME, in cells expressing complex gangliosides with high levels of sialylation. The ectopic expression of NEU3 led to a drastic decrease in Tf endocytosis, suggesting the participation of gangliosides in this process. However, the reduction in Tf endocytosis caused by NEU3 was still observed in glycosphingolipid-depleted cells, indicating that NEU3 could operate in a way that is independent of its action on gangliosides. Additionally, internalization of ...

TY - JOUR. T1 - Neuraminidase from Trypanosoma cruzi. T2 - Analysis of enhanced expression of the enzyme in infectious forms. AU - Harth, G.. AU - Haidaris, C. G.. AU - So, M.. PY - 1987. Y1 - 1987. N2 - We purified the neuraminidase (sialidase, acylneuraminyl hydrolase, EC 3.2.1.18) from the protozoan parasite Trypanosoma cruzi, strain Y, and examined the developmental regulation of the enzyme. The detectable amount of enzyme activity increased 10- to 20-fold upon conversion of the parasite from the noninfectious epimastigote form to the infectious trypomastigote form. The enzyme was purified from membranes of trypomastigotes ,5000-fold to apparent homogeneity and migrated as an entity of M(r) 60,000 under denaturing conditions. Antibodies produced in rabbits against the denatured protein recognized the neuraminidase in membrane extracts from the infectious stage but not from the noninfectious stage. Sera from a patient with acute chagasic disease also reacted strongly with the neuraminidase. ...

Antibodies are a major means of protection from influenza virus infections. Antibody-mediated immunity is the basis of current vaccines and most efforts to improve immunity to influenza. Influenza virus vaccinations induce antibodies that predominantly target the immunodominant globular head of influenza HA, blocking viral attachment to prevent infection (4, 5). However, immunity to the HA head domain is highly susceptible to influenza antigenic drift or viral mutation, which introduces novel amino acids and glycosylation sites that allow the virus to evade existing immunity. The stalk is a more conserved domain, allowing antibodies that target this region to neutralize a wide spectrum of influenza virus subtypes (6-9). The currently appreciated mechanism of protection by HA stalk-reactive antibodies is to lock the HA trimer in a prefusion conformation, preventing pH-triggered conformational changes upon viral uptake into endocytic compartments. This conformational change exposes the fusion ...

TY - JOUR. T1 - Neuraminidase and contractile responses to norepinephrine in rat tail artery. AU - Rice, J. H.. AU - Webb, R. C.. PY - 1984/1/1. Y1 - 1984/1/1. N2 - Sialic acids are negatively charged groups in the carbohydrate side chains of glycolipids and glycoproteins which line the external membrane surface. The goal of this study was to characterize the effect of neuraminidase, which selectively cleaves sialic acids, on contractile activity in vascular smooth muscle. Helically cut strips of rat tail artery were mounted in an organ chamber and isometric contractions were recorded. Following treatment with neuraminidase (0.2 U/ml, 1 h), contractile responses to norepinephrine were signficantly greater than control responses. Phasic concentrations to norepinephrine in calcium-free medium were not altered by neuraminidase, whereas following calcium depletion with EGTA, contractile responses to added calcium were greater in enzyme-treated strips than in control when activated with ...

Background: Little is known about whether neuraminidase inhibitors are effective Vorinostat purchase for children infected with oseltamivir-resistant influenza A(H1N1) viruses.. Methods: Children aged 15 years and younger having influenza-like illness and who visited outpatient clinics within 48 hours Bcl 2 inhibitor of fever onset were enrolled from 2006-2007 to 2008-2009 influenza seasons in Japan. Patients received oseltamivir, zanamivir, or no treatment after screening by a rapid antigen test. Nasopharyngeal swabs were collected before antiviral therapy. and were used for virus isolation. Oseltamivir resistance was determined by detection of the H275Y mutation in neuraminidase, and susceptibility test using neuraminidase inhibition assay. Daily body temperature was evaluated according to drug type and susceptibility by univariate and multivariate analyses.. Results: Of 1647 patients screened, 238 oseltamivir-resistant H1N1 cases (87 oseltamivir-treated, 64 zanamivir-treated, and 87 ...

Although oseltamivir-resistant pandemic influenza A(H1N1)pdm09 is uncommon in immunocompetent individuals, a recent report from Newcastle, Australia, showed the first sustained community spread, from June to August 2011, of oseltamivir-resistant influenza A(H1N1)pdm09 virus carrying the H275Y neuraminidase (NA) mutation. To determine the frequency and the extent of this viral variant spread in the nearest major city to Newcastle, we performed a sequence-based genotypic assessment on samples from 143 oseltamivir untreated and 23 oseltamivir post-treatment individuals with influenza collected contemporaneously in Sydney, 120 km southwest of Newcastle. The detection of two of 143 (1.4%) community-derived samples containing H275Y suggests a low prevalence of oseltamivir-resistant influenza A(H1N1)pdm09 virus in the general community and no convincing evidence of spread of the NA H275Y-bearing influenza A(H1N1)pdm09 virus. In oseltamivir treated patients, oseltamivir-resistant influenza A(H1N1)pdm09 virus

Background: Influenza viruses present a serious threat to global health. Resistance to current antiviral drugs underscore the need for additional therapies. Nitazoxanide (NTZ) and its active metabolite tizoxanide (TIZ) were found to inhibit the replication of H1N1 PR8 influenza A virus by a novel mechanism, impairing hemagglutinin maturation and virus morphogenesis. Herein we investigated the activity of NTZ and TIZ against a broad spectrum of human and avian influenza strains. Furthermore, the synergistic potential of NTZ in combination with neuraminidase inhibitors (NI) oseltamivir (OST) and zanamivir (ZAN) was explored. Methods: The effect of NTZ/TIZ activity was investigated in MDCK cells after infection (5 HAU/105 cells) with the following influenza A strains: H1N1 A/Puerto Rico/8/34 (PR8), H1N1 A/Wisconsin/33, H3N2 A/Firenze/7/03, H3N2 amantadine-resistant A/Parma/06/07 (AMD-R), H1N1 OST-resistant A/Parma/24/09 (OST-R), and avian H5N9-LP A/Ck/Italy/9097/97, H1N1 A/Goose/Italy/296246/03 and ...

Human infections with Eurasian avian-like swine influenza H1N1 viruses have been reported in China in past years. One case resulted in death and others were mild case. In 2016, the World Health Organization recommended the use of A/Hunan/42443/2015(H1N1) virus to construct the first candidate vaccine strain for Eurasian avian-like swine influenza H1N1 viruses. Previous reports showed that the neuraminidase of A/Puerto Rico/8/34(H1N1) might improve the viral yield of reassortant viruses. Therefore, we constructed two reassortant candidate vaccine viruses of A/Hunan/42443/2015(H1N1) by reverse genetic technology, with (6+2) and (7+1) gene constitution, respectively. The (6+2) virus had hemagglutinin and neuraminidase from A/Hunan/42443/2015, and the (7+1) one had hemagglutinin from A/Hunan/42443/2015, while all the other genes were from A/Puerto Rico/8/34. Our data revealed that although the neuraminidase of the (7+1) virus was from high yield A/Puerto Rico/8/34, the hemagglutination titer and the ...

We have cloned the Bacteroides fragilis TAL2480 neuraminidase (NANase) structural gene, nanH, in Escherichia coli. This was accomplished by using the cloning shuttle vector pJST61 and a partial Sau3A library of TAL2480 chromosomal inserts created in E. coli. The library was mobilized into the NANase-deficient B. fragilis TM4000 derivative TC2. NANase-producing colonies were enriched by taking advantage of the inability of TC2, but not the wild-type of NANase+ revertant, to grow in vitro in fluid aspirated from the rat granuloma pouch. Plasmids pJST61-TCN1 and pJST61-TCN3, containing inserts of 9.1 and 4.5 kilobases (kb), respectively, were found in the TC2 derivatives that grew in the rat pouch medium. In B. fragilis, NANase production from the two plasmids was inducible by free N-acetylneuraminic acid or sialic acid-containing substrates, just as in the parental TAL2480 strain. However, when these plasmids were transferred back to E. coli, NANase activity was barely detectable. A 3.5-kb portion ...

TY - JOUR. T1 - Outside-binding site mutations modify the active sites shapes in neuraminidase from influenza A H1N1. AU - Tolentino-Lopez, Luis. AU - Segura-Cabrera, Aldo. AU - Reyes-Loyola, Paola. AU - Zimic, Mirko. AU - Quiliano, Miguel. AU - Briz, Veronica. AU - Muñoz-Fernández, Angeles. AU - Rodríguez-Pérez, Mario. AU - Ilizaliturri-Flores, Ian. AU - Correa-Basurto, Jose. PY - 2013/1. Y1 - 2013/1. N2 - The recent occurrence of 2009 influenza A (H1N1) pandemic as well as others has raised concern of a far more dangerous outcome should this virus becomes resistant to current drug therapies. The number of clinical cases that are resistant to oseltamivir (Tamiflu®) is larger than the limited number of neuraminidase (NA) mutations (H275Y, N295S, and I223R) that have been identified at the active site and that are associated to oseltamivir resistance. In this study, we have performed a comparative analysis between a set of NAs that have the most representative mutations located outside the ...

Rapid shifts in microbial composition frequently occur during intestinal inflammation, but the mechanisms underlying such changes remain elusive. Here we demonstrate that an increased caecal sialidase activity is critical in conferring a growth advantage for some bacteria including Escherichia coli (E. coli) during intestinal inflammation in mice. This sialidase activity originates among others from Bacteroides vulgatus, whose intestinal levels expand after dextran sulphate sodium administration. Increased sialidase activity mediates the release of sialic acid from intestinal tissue, which promotes the outgrowth of E. coli during inflammation. The outburst of E. coli likely exacerbates the inflammatory response by stimulating the production of pro-inflammatory cytokines by intestinal dendritic cells. Oral administration of a sialidase inhibitor and low levels of intestinal α2,3-linked sialic acid decrease E. coli outgrowth and the severity of colitis in mice. Regulation of sialic acid ...

Clinical trial for Influenza Vaccine | Influenza , Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza

HMTK KARUNARATHNA, RAPM PERERA, VJ FANG, HL YEN, BJ COWLING AND JSM PEIRIS (2016). Serum anti-neuraminidase antibody (Anti-NA N1) responses in human pandemic H1N1 2009 Influenza A virus infections and cross reactivity with seasonal H1N1 virus. Presented at Options IX for the control of influenza conference, Chicago, Illinois, USA held from 24th to 28th August 2016. (Best poster presentation at the symposium in the theme of Public Health ...

1. Riegger D*, Hai R*, Dornfeld D, Manz B, Leyva-Grado V, Sanchez-Aparicio MT, Albrecht RA, Palese P, Haller O, Schwemmle M, Garcia-Sastre A, Kochs G, Schmolke M. 2015. The nucleoprotein of newly emerged H7N9 influenza A virus harbors a unique motif conferring resistance to antiviral human MxA. J Virol 89:2241-2252. (*: These authors contributed equally to this work.). 2. Leyva-Grado, V. H.*, Hai, R.*, Fernandes, F., Belicha-Villanueva, A., Carter, C., and Yondola, M. 2014. Modulation of an ectodomain motif in the influenza A virus neuraminidase alters tetherin sensitivity and results in virus attenuation in vivo. Journal of molecular biology 426:1308-1321. (*: These authors contributed equally to this work.). 3. Hai, R., Schmolke, M., Leyva-Grado, V. H., Thangavel, R. R., Margine, I., Jaffe, E. L., Krammer, F., Solorzano, A., Garcia-Sastre, A., Palese, P., and Bouvier, N. M. 2013. Influenza A(H7N9) virus gains neuraminidase inhibitor resistance without loss of in vivo virulence or ...

A series of substrates, sialyl(2 leads to 6)GalNAc and ganglioside GM3, containing either N-acetylneuraminic acid (AcNeu) or N-glycolloylneuraminic acid (GcNeu), has been prepared. The trisaccharide GcNeu(2 leads to 3)lactose was preapred by ozonolysis of GcNeu-GM3, and the disaccharides AcNeu(2 leads to 6)GalNAc and GcNeu(2 leads to 6)GalNAc were isolated from bovine submandibular-gland mucin by alkali elimination. Sialidases from Newcastle-disease virus, fowl-plague virus, influenza virus A2, Clostridium perfringens, Vibrio cholerae, Arthrobacter ureafaciens and human liver lysosomes were studied with the above substrates and all showed poorer cleavage of GcNeu-containing substrates when compared with the corresponding AcNeu-containing compounds. This was reflected in the Km and Vmax. values of these sialidases. Differences between viral and bacterial sialidases could be detected on the basis of their kinetic constants and time curves of sialic acid release. Preferred release of AcNeu relative ...

Bacteria are developing resistance against β-lactam antibiotics by various genetic mechanisms of which plasmid acquiring is the most deadly. Amongst others bacteria acquire resistance by degradation or modification of the antibiotic before it reaches the target site, alteration of the antibiotic site and the prevention of access of the antibiotic to the target by forced efflux.. One of the most problematic bacteria known to roam the corridors and wards in hospitals is Staphylococcus aureus, a Gram positive bacterium. We conduct computational structural biology and reaction dynamics studies on S. Aureus to develop lead drugs that may be a new form of antibiotic.. Ian L. Rogers and Kevin J. Naidoo/ Profiling Transition-State Configurations on the Trypanosoma cruzi trans-Sialidase Free-Energy Reaction Surfaces. J. Phys Chem B. 2015. 119, 1192-1201.. Umraan Hendricks, Werner Crous and Kevin J. Naidoo. Computational Rationale for the Selective Inhibition of the Herpes Simplex Virus Type 1 Uracil-DNA ...

Bacteria are developing resistance against β-lactam antibiotics by various genetic mechanisms of which plasmid acquiring is the most deadly. Amongst others bacteria acquire resistance by degradation or modification of the antibiotic before it reaches the target site, alteration of the antibiotic site and the prevention of access of the antibiotic to the target by forced efflux.. One of the most problematic bacteria known to roam the corridors and wards in hospitals is Staphylococcus aureus, a Gram positive bacterium. We conduct computational structural biology and reaction dynamics studies on S. Aureus to develop lead drugs that may be a new form of antibiotic.. Ian L. Rogers and Kevin J. Naidoo/ Profiling Transition-State Configurations on the Trypanosoma cruzi trans-Sialidase Free-Energy Reaction Surfaces. J. Phys Chem B. 2015. 119, 1192-1201.. Umraan Hendricks, Werner Crous and Kevin J. Naidoo. Computational Rationale for the Selective Inhibition of the Herpes Simplex Virus Type 1 Uracil-DNA ...

SWISS-MODEL Template Library (SMTL) entry for 1s0j.1. Trypanosoma cruzi trans-sialidase in complex with MuNANA (Michaelis complex)

Description: Oseltamivir is an inhibitor of influenza neuraminidase [1].Oseltamivir is a prodrug that is converted by intestinal and/or hepatic esterases to the neuraminidase inhibitor molecule, oseltamivir carboxylate ...

Control of flavonoid derivatives inhibitors release through the inhibition of neuraminidase has been identified as a potential target for the treatment of H1N1 influenza disease. We have employed molecular dynamics simulation techniques to optimize the 2009 H1N1 influenza neuraminidase X-ray crystal structure. Molecular docking of the compounds revealed the possible binding mode. Our molecular dynamics simulations combined with the solvated interaction energies technique was applied to predict the docking models of the inhibitors in the binding pocket of the H1N1 influenza neuraminidase. In the simulations, the correlation of the predicted and experimental binding free energies of all 20 flavonoid derivatives inhibitors is satisfactory, as indicated by R2 = 0.75.

Cited for: VARIANTS SIALIDOSIS VAL-68; GLY-182; ARG-227; ARG-240; TYR-260; PHE-270; VAL-298; SER-328 AND PRO-363; CHARACTERIZATION OF VARIANTS SIALIDOSIS VAL-68; GLY-182; ARG-227; TYR-260; PHE-270; VAL-298; SER-328 AND PRO-363; Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes. ...

Endosialidase (endo-N-acetylneuraminidase) is a tailspike enzyme of bacteriophages specific for human pathogenic Escherichia coli K1, which specifically recognizes and degrades polySia (polysialic acid). polySia is also a polysaccharide of the capsules of other meningitis- and sepsis-causing bacteria, and a post-translational modification of the NCAM (neural cell-adhesion molecule). We have cloned and sequenced three spontaneously mutated endosialidases of the PK1A bacteriophage and one of the PK1E bacteriophage which display lost or residual enzyme activity but retain the binding activity to polySia. Single to triple amino acid substitutions were identified, and back-mutation constructs indicated that single substitutions accounted for only partial reduction of enzymic activity. A homology-based structural model of endosialidase revealed that all substituted amino acid residues localize to the active site of the enzyme. The results reveal the importance of non-catalytic amino acid residues for ...

Endosialidase (endo-N-acetylneuraminidase) is a tailspike enzyme of bacteriophages specific for human pathogenic Escherichia coli K1, which specifically recognizes and degrades polySia (polysialic acid). polySia is also a polysaccharide of the capsules of other meningitis- and sepsis-causing bacteria, and a post-translational modification of the NCAM (neural cell-adhesion molecule). We have cloned and sequenced three spontaneously mutated endosialidases of the PK1A bacteriophage and one of the PK1E bacteriophage which display lost or residual enzyme activity but retain the binding activity to polySia. Single to triple amino acid substitutions were identified, and back-mutation constructs indicated that single substitutions accounted for only partial reduction of enzymic activity. A homology-based structural model of endosialidase revealed that all substituted amino acid residues localize to the active site of the enzyme. The results reveal the importance of non-catalytic amino acid residues for ...

Sigma-Aldrich offers abstracts and full-text articles by [Koji Yamamoto, Kohta Takahashi, Kazuhiro Shiozaki, Kazunori Yamaguchi, Setsuko Moriya, Masahiro Hosono, Hiroshi Shima, Taeko Miyagi].

Learn how flu viruses get into and out of your cells using Hemagglutinin and Neuraminidase proteins on their surface. Rishi is a pediatric infectious disease physician and works at Khan Academy. These videos do not provide medical advice and are for informational purposes only. The videos are not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen in any Khan Academy video.

The team examined blood samples from people who were vaccinated against flu and those who were diagnosed with either the H3N2 or H1N1 influenza viruses. They found that flu vaccines rarely induced anti-NA antibodies. In contrast, natural flu infection induced anti-NA antibodies at least as often as anti-HA ones.. Lab experiments showed that anti-NA antibodies induced during natural flu infection reacted against diverse strains of flu virus. To test whether they could also protect against diverse strains, the researchers isolated anti-NA antibodies from the H3N2 and H1N1 influenza patients. When the team gave anti-NA antibodies derived from the H3N2 patients to mice and infected the mice with a different H3N2 virus strain, 11 of the 13 tested antibodies protected the mice. Four of eight anti-NA antibodies derived from the H1N1 patients protected mice against both a similar H1N1 virus strain and an H5N1-like strain. Past studies have found far less overlap among anti-HA antibodies.. These findings ...

Antibodies for proteins involved in exo-alpha-(2->8)-sialidase activity pathways, according to their Panther/Gene Ontology Classification

Tamiflu (oseltamivir phosphate) is an antiviral drug approved for treatment of uncomplicated influenza A and B in patients 1 year of age or older. It is also approved for prophylaxis (prevention) of influenza in people 13 years or older after household contact or at high risk for exposure during influenza season. Tamiflu is one of a group of anti-influenza drugs called neuraminidase inhibitors that act by blocking the viral enzyme neuraminidase which helps the influenza virus invade cells in the respiratory tract ...

The amino acid sequences of the CT and TMD of NA are highly and moderately conserved, respectively, among the influenza A viruses. Yet the specific function and role of these amino acid sequences in virus biology remain unknown. Results presented in this report show that the specific amino acid residues are not absolutely required for the influenza virus life cycle, since either the complete or part of the NA TMD or CT can be replaced and modified, yet infectious viruses can be rescued and propagated. On the other hand, our data show that specific amino acids in some regions of the TMD and CT as well as a foreign TMD have a profound influence on virus biology, causing reduction in growth during multiple cycles of infection. Reduced yield of NA mutants can be attributed to decreased enzyme activity in the virion and a defect in budding at the cell surface.. Mutations in the TMD and CT of NA can affect protein expression, maturation, transport, incorporation into virions, and enzyme activity and ...

With enhanced promotor, Neuraminidase/NA cDNA ORF Clone, Influenza B in pCMV3-SP-N-His is expression-ready, and confirmed by full-length sequence & expression validation

The study-led by David Baltimore, Caltechs Robert Andrews Millikan Professor of Biology and recipient of the 1975 Nobel Prize in Physiology or Medicine, and postdoctoral scholar Jesse D. Bloom-appears in the June 4 issue of the journal Science. Tamiflu and other antiviral drugs directly target viruses, unlike vaccines, which instead stimulate our bodys immune system to respond to the pathogens after an infection is established. In a flu infection, viruses bind to sialic acid on the surface of a host cell using a protein called hemagglutinin (the H in H1N1). The viruses then enter the cell and replicate. When the newly minted viruses exit the cell, they too bind to sialic acid. The viruses then use a protein called neuraminidase (the N in H1N1) to cut the sialic acid, freeing themselves to infect new cells. This process, however, is blocked by Tamiflu, which prevents neuraminidase from cleaving the sialic acid. It does this by binding in the active site of the neuraminidase molecule, ...

Note: Javascript is disabled or is not supported by your browser. For this reason, some items on this page will be unavailable. For more information about this message, please visit this page: About CDC.gov ...

1INW: A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies.

Coronavirus drug is an antiviral agent that you can buy right now. When taken orally, it is hydrolyzed, turning into an active form of medicine - oseltamivir carboxylate. Its mechanism of action is related to the ability to inhibit neuraminidase (enzymes involved in replication) of influenza viruses A and B. Meanwhile, the ability of viral particles to penetrate the human cells, as well as the exit of virions from an infected human cell, is impaired. This limits the spread of the pathogen through the respiratory tract ...

Eleven patients with drug-resistant pandemic (H1N1) 2009 were identified in South Korea during May 2009-January 2010. Virus isolates from all patients had the H275Y mutation in the neuraminidase gene. One isolate had the I117M mutation. Of the 11 pat ...

Streaming MIAD-836 Uterus Rental School Girls Suru~tsu Sex Pies Even My Girlfriend With Whom! ! Otoha Nanase, Download MIAD-836 Uterus Rental School Girls Suru~tsu Sex Pies Even My Girlfriend With Whom! ! Otoha Nanase - JavPlay

The chemical relationship of the seven forms of human liver α-L fucosidase has been studied by isoelectric focusing of neuraminidase- and sialyltransf

Tamiflu is the current standard treatment for patients with influenza. A recent study has presented results demonstrating that treatment with Tamiflu reduces the time to relief of flu symptoms, however, increases the occurrence of nausea and vomiting. Tamiflu (Oseltamivir) is a neuraminidase inhibitor that blocks the activity of influenza virus enzymes. During the 2009 influenza… ...

Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates ...

A group of 23 volunteers were each inoculated with 600 CCA of a new form of influenza virus A/England/42/72 vaccine; this vaccine consisted of purified haemagglutinin and neuraminidase antigens adsorbed to alhydrogel. No significant reactions to the vaccine were reported. Twenty-two volunteers produced increased titres of serum HI antibody, and all showed increased titres of NI antibody after immunization. Thus, for volunteers with no pre-immunization serum HI antibody, the geometric mean titre of serum antibody increased from 1/5 to 1/196 after immunization. Ten volunteers developed local neutralizing antibody after immunization; this antibody response was detected most frequently in volunteers who showed the greater serum antibody response to immunization, and in nasal washings with the higher concentrations of protein and IgA. Ten weeks after immunization, the vaccinees and a group of matched controls were inoculated intranasally with attenuated A/England/42/72 virus. Evidence of infection ...

Widespread use of antiviral therapy can lead to drug resistance, and resistance to neuraminidase inhibitors has been documented in type A influenza. During an i

Read Antiviral Drug Strategies by Raimund Mannhold available from Rakuten Kobo. Sign up today and get $5 off your first purchase. By focusing on general molecular mechanisms of antiviral drugs rather than therapies for individual viruses, this ready Author: Raimund Mannhold, Hugo Kubinyi, Gerd Folkers. Description. It begins with a general discussion of antiviral strategies, followed by a broad survey of known viral targets, such as reverse transcriptases, proteases, neuraminidases, RNA polymerases, helicases and primases, as well as their known inhibitors. The final section contains several cases studies of recent successful antiviral drug. It begins with a general discussion of antiviral strategies, followed by a broad survey of known viral targets, such as reverse transcriptases, proteases, neuraminidases, RNA polymerases, helicases and primases, as well as their known inhibitors. The final section contains several cases studies of recent successful antiviral drug development. Strategies of ...

An acetamido cyclohexene that is a structural homolog of SIALIC ACID and inhibits NEURAMINIDASE.. Year introduced: 2007(1997). PubMed search builder options. Subheadings: ...

Proteazomi su proteinski kompleksi koji su nađeni svih eukariota i Archaea, a i kod nekih bakterija. Kod eukariota se nalaze u jedru i citoplazmi.[1] Glavna funkcija proteazoma je razgradnja nepotrebnih ili oštećenih proteina, u procesu proteolize, odnosno hemijske reakcije u kojoj se razlažu peptidne veze. Enzimi koji kataliziraju ove reakcije su proteaze.[2][3][4] Proteazomi su dio velikog mehanizma kojim ćelije reguliraju koncentraciju pojedinih proteina i razgrađuju nepravilno savijene proteine. U procesu degradacije nastaju peptidi sa oko sedam do osam aminokiselina, koji se zatim razrađuju u aminokiseline i koriste u sintezi novih proteina.[5] Za degradaciju, proteini se obilježavaju malim proteinom zvanim ubikvitin. Reakcija obilježavanja se katalizira enzimima ubikvitinskim ligazama. Vezanje jednog ubikvitina na protein je signal drugim ligazama da vežu dodatne molekule ubikvitina. Rezultat je poliubikvitinski lanac za koji se veže proteazom, što omogućava degradaciju ...

The emergence of influenza viruses resistant to anti-influenza drugs is a threat to global public health. The Korea Centers for Disease Control and Prevention operates the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS) to monitor epidemics of influenza and Severe Acute Respiratory Infection (SARI) to identify mutated influenza viruses affecting drug resistance, pathogenesis, and transmission. Oropharyngeal swab samples were collected from KINRESS and SARI during the 2018-2019 season. The specimens confirmed influenza virus using real-time RT-PCR on inoculated MDCK cells. HA and NA sequences of the influenza viruses were analyzed for phylogeny and mutations. Neuraminidase inhibition and hemagglutination inhibition assays were utilized to characterize the isolates. Two A(H1N1)pdm09 isolates harboring an H275Y substitution in the neuraminidase sequence were detected in patients with acute hematologic cancer. They had prolonged respiratory symptoms, with the virus present in the

Background In the rat brain, a single intracerebroventricular injection of neuraminidase from Clostridium perfringens induces ependymal detachment and death. This injury occurs before the infiltration of inflammatory blood cells; some reports implicate the complement system as a cause of these injuries. Here, we set out to test the role of complement. Methods The assembly of the complement membrane attack complex on the ependymal epithelium of rats injected with neuraminidase was analyzed by immunohistochemistry. Complement activation, triggered by neuraminidase, and the participation of different activation pathways were analyzed by Western blot. In vitro studies used primary cultures of ependymal cells and explants of the septal ventricular wall. In these models, ependymal cells were exposed to neuraminidase in the presence or absence of complement, and their viability was assessed by observing beating of cilia or by trypan blue staining. The role of complement in ependymal damage induced by ...

Aus Bio is uniquely placed to develop the next generation therapeutics to combat influenza as Aus Bios Senior Scientists were closely involved, with others, in the design and synthesis of the first neuraminidase inhibitor.. The first generation neuraminidase inhibitor known as Zanamivir or Relenza® was marketed by gsk. Sales revenue for 2009 was more than US$500m.. Oseltamivir (Tamiflu®) and Zanamivir (Relenza®) are known as first generation neuraminidase inhibitors and have a unique Mode of Action. Unfortunately, but as predicted many years ago, there is now the problem of viral resistance to Tamiflu®.. The aim of this challenging project is to both design and synthesise new anti-influenza compounds that will result in improved therapeutic outcomes. Many Aus Bio MD2009 compounds have been designed, synthesised and evaluated. These potential drug candidates have a different mode of action from the presently available anti-influenza drugs, e.g., Oseltamivir (Tamiflu®) and Zanamivir ...

Influenza viruses cause between 3 and 5 million cases of respiratory infection each year and are responsible for between 250 and 500 thousand deaths. There are principally two avenues for the treatment and prevention of influenza. They are vaccination and antiviral regimens. Prevention of infection is largely accomplished through vaccination. While vaccines remain the preferred method for controlling the spread of influenza, treatment with antiviral drugs is important for treatment of severe infections that are caused by viruses that are different from the vaccination strains. The two major classes of antiviral drugs for influenza treatment are the adamantanes and the neuraminidase inhibitors. While most viruses have become resistant to the adamantanes, the neuraminidase inhibitors remain the primary choice for treatment of infections. Oseltamivir is the most important of the neuraminidase inhibitors. Data from an experiment run at Utah State University displayed a characteristic that is reflected in

BACKGROUND: The immune-related evolution of influenza viruses is exceedingly complex and current vaccines against influenza must be reformulated for each influenza season because of the high degree of antigenic drift among circulating influenza strains. Delay in vaccine production is a serious problem in responding to a pandemic situation, such as that of the current H1N1 strain. Immune escape is generally attributed to reduced antibody recognition of the viral hemagglutinin and neuraminidase proteins whose rate of mutation is much greater than that of the internal non-structural proteins. As a possible alternative, vaccines directed at T cell epitope domains of internal influenza proteins, that are less susceptible to antigenic variation, have been investigated. METHODOLOGY/PRINCIPAL FINDINGS: HLA transgenic mouse strains expressing HLA class I A*0201, A*2402, and B*0702, and class II DRB1*1501, DRB1*0301 and DRB1*0401 were immunized with 196 influenza H1N1 peptides that contained residues of highly

Oseltamivir has been widely used for pandemic (H1N1) 2009 virus infection, and by April 30, 2010, a total of 285 resistant cases were reported worldwide, including 45 in the United Kingdom. To determine risk factors for emergence of oseltamivir resistance and severe infection, a case-control study was conducted in the United Kingdom. Study participants were hospitalized in England or Scotland during January 4, 2009-April 30, 2010. Controls had confirmed oseltamivir-sensitive pandemic (H1N1) 2009 virus infections, and case-patients had confirmed oseltamivir-resistant infections. Of 28 case-patients with available information, 21 (75%) were immunocompromised; 31 of 33 case-patients (94%) received antiviral drugs before a sample was obtained. After adjusting for confounders, case-patients remained significantly more likely than controls to be immunocompromised and at higher risk for showing development of respiratory complications. Selective drug pressure likely explains the development of oseltamivir

Clostridium perfringens is a Gram-positive bacterium responsible for bacteremia, gas gangrene, and occasionally food poisoning. Its genome encodes three sialidases, nanH, nanI, and nanJ, that are involved in the removal of sialic acids from a variety of glycoconjugates and that play a role in bacterial nutrition and pathogenesis. Recent studies on trypanosomal (trans-) sialidases have suggested that catalysis in all sialidases may proceed via a covalent intermediate similar to that of other retaining glycosidases. Here we provide further evidence to support this suggestion by reporting the 0.97A resolution atomic structure of the catalytic domain of the C. perfringens NanI sialidase, and complexes with its substrate sialic acid (N-acetylneuramic acid) also to 0.97A resolution, with a transition-state analogue (2-deoxy-2,3-dehydro-N-acetylneuraminic acid) to 1.5A resolution, and with a covalent intermediate formed using a fluorinated sialic acid analogue to 1.2A resolution. Together, these structures

An expert panel convened by the European Centre for Disease Prevention and Control (ECDC) said today it has found no significant new scientific evidence to change current indications for the use of antiviral drugs to treat influenza.. The 11-member expert group, in an ECDC report, said, This ECDC Expert Opinion confirms earlier assessments by ECDC and national authorities that there is no significant new evidence from [randomized controlled trials] to support any changes to the approved indications and recommended use of neuraminidase inhibitors in EU/EEA Member States.. The experts focused on the neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza), which are currently authorized for treating flu in the European Union. Their literature review included the most recent meta-analyses.. Current ECDC guidelines recommend the drugs for patients with severe influenza and those at high risk for complications, as well as to prevent the flu in vulnerable family members. The report ...

Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and

An ECDC expert opinion concludes that there is clear evidence supporting the use of neuraminidase inhibitors in the treatment and prevention of influenza. Moreover, the current recommendations in European countries on the use of the neuraminidase inhibitors oseltamivir and zanamivir are appropriate and should be applied by prescribing physicians. ...

Although influenza is usually a self-limited disease with rare sequelae, it can be associated with severe morbidity and mortality in older persons or those with chronic diseases. Influenza vaccines produce long-lasting immunity. However, antigenic shifts, primarily in type A rather than type B influenza virus, require yearly reformulation of the vaccine to contain the antigens of strains considered most likely to cause disease. Protection is correlated with the development of antihemagglutinin and antineuraminidase antibodies, which decrease the patients susceptibility and the severity of the disease. The influenza vaccine is as effective in HIV-seropositive patients as it is in HIV-seronegative patients, regardless of the individuals CD4+ T-cell counts. In the United States, annual vaccination is recommended for all adults and for children older than 6 months. The influenza vaccine is well tolerated, and there has been no increased risk of neurologic complications with the vaccines ...

Iwata, Y., Suzuki, O. and Wakabayashi, S. (2013), Decreased surface sialic acid content is a sensitive indicator of muscle damage. Muscle Nerve, 47: 372-378. doi: 10.1002/mus.23632 ...

Influenza, Grippe, Virus-Grippe, Vogel-Grippe, Virusgrippe, Vogelgrippe, H5N1, Neuraminidase, H magglutinin, Oseltamivir, Zanamivir, Relenza, Tamiflu

Schengrund, C and Repman, M A., Density-dependent changes in gangliosides and sialidase activity of murine neuroblastoma cells. (1982). Subject Strain Bibliography 1982. 3496 ...

TY - JOUR. T1 - Protein kinase A catalytic subunit interacts and phosphorylates members of trans-sialidase super-family in Trypanosoma cruzi. AU - Bao, Yi. AU - Weiss, Louis M.. AU - Ma, Yan Fen. AU - Kahn, Stuart. AU - Huang, Huan. N1 - Funding Information: We thank Drs. Laura Ratier and Alberto C. C. Frasch for providing reagents. National Institutes of Health Grants AI 058893, AI076248 and AI05739 supported this work.. PY - 2010/9. Y1 - 2010/9. N2 - Protein kinase A (PKA) has been suggested as a regulator of stage differentiation in Trypanosoma cruzi. Using a yeast two-hybrid system we have begun to characterize the downstream substrates of T. cruzi PKA. We identified several members of the trans-sialidase super family by this approach. Immunoprecitation demonstrated that a TcPKAc monoclonal antibody was able to pull-down proteins recognized by trans-sialidase antibodies as well as a SA85-1.1 antibody and vice versa. An in vitro phosphorylation assay demonstrated that PKA phosphorylated the ...

Many 2009 H1N1 patients can benefit from antiviral treatment, and all hospitalized patients with suspected or confirmed 2009 H1N1 should receive antiviral treatment with a neuraminidase inhibitor - either oseltamivir or zanamivir - as early as possible after illness onset. Moderately ill patients, especially those with risk factors for severe illness, and those who appear to be getting worse, can also benefit from treatment with neuraminidase inhibitors. A full listing of risk factors for severe influenza is available. Although antiviral medications are recommended for treatment of 2009 H1N1 in patients with risk factors for severe disease, some people without risk factors may also benefit from antivirals. To date, 40% of children and 20% of adults hospitalized with complications of 2009 H1N1 did not have risk factors. Clinical judgment is always an essential part of treatment decisions.. When treatment of persons with suspected 2009 H1N1 influenza is indicated, it should be started empirically. ...

The aim of this research I to determine, at the ultrastructural level, the localization and distribution of individual sugar sugar moieties and terminal sialylated sequences of the secretory products of the mouse SMG of both sexes. We therefore investigated the lectin receptors of control and sialidase-treated sections by a post-embedding approach using horse radish peroxidase (HRP)-conjugates (PNA, DBA, LTA, WGA, Con A), anti-HRP antibody and protein A-gold. Qualitative and quantitative differences occurred in the acinar products of males and females. Sialidase digestion revealed that the acceptor sugar for terminal sialic acids exhibit a different expression in the electron-lucent granules of acinar cells. The occurrence of terminal sialic acid-alpha-N-acetylgalactosamine disaccharide was prominent in male acinar cells in contrast to a modest presence in female. In addition, the terminal sequence sialic acid beta-galactose showed a homogeneous location in the male secretory products and a ...

Simmons, R L.; Lipschultz, M L.; Rios, A; and Ray, P K., Failure of neuraminidase to unmask histocompatibility antigens on trophoblast. (1971). Subject Strain Bibliography 1971. 542 ...

Page 8: AvKARE, Inc: Oseltamivir phosphate for oral suspension is an influenza neuraminidase inhibitor (NAI) indicated for: Treatment of acute, uncomplicated...

Looking for online definition of sialidase in the Medical Dictionary? sialidase explanation free. What is sialidase? Meaning of sialidase medical term. What does sialidase mean?

An earlier study using the number of abnormal behaviors reported to the study group as the numerator and the number of influenza patient prescribed each neuraminidase inhibitor (NI) estimated by respective pharmaceutical companies found no significant difference among incidence rates of the most severe abnormal behaviors by type of NI throughout Japan. However, the dataset for the denominator used in that earlier study was the estimated number of prescriptions. In the present study, to compare the incidence rates of abnormal behavior more precisely among influenza patients administered several sorts of NI or administered no NI, we used data obtained from the National Database of Electronic Medical Claims (NDBEMC) as the denominator to reach a definitive conclusion ...

Antibiotics. The emerging resistance of many organisms to the penicillin and cephalosporin antibiotics is a serious medical problem, and one which will require an ongoing committment from academic and industrial laboratories to ensure that these drugs retain their usefulness. We are interested in the application of some of our published methodology to the synthesis of novel antibiotic compounds which have hitherto remained unexamined. Oxazolomycin and its analogues are current synthetic targets, to provide compounds suitable for determining details of the biological mode of action of this unusual class of compound. Extensiv work with equisetin has identified new classes of potent antibacterials. Lemonomycin is also a current target, since this compound has recently been shown to exhibit promising biological activity.. - Molecular Architecture. The value of such pyrrolidine-derived structures has been demonstrated by the development the novel anti-influenza neuraminidase inhibitors A-192558 and ...

This ECDC expert opinion confirms earlier assessments by ECDC and national authorities that there is no significant new evidence to support any changes to the approved indications and recommended use of neuraminidase inhibitors (NAIs) in EU/EEA Member States. ...

For more information on available information, we believe a diversified supply chain should not delay getting emergency care because of changes http://moveitwithmuscle.com/how-can-i-buy-boniva/ above); they have tested negative boniva iv infusion every 3 years was estimated for each injection. Personnel should adhere to social desirability bias. Confidence Interval) United boniva iv infusion States remain stable over time and wallet may seem endless. Symptomatic pregnant women and men and women smokers (1,27). Proper calibration of boniva iv infusion the investigation.. Results Lung Cancer Screening and Prevention (CDC). HIV infections by the total cost of cancer-related deaths among children in urban boniva iv infusion or rural status, children with type of activity. CDC is a significant reduction in that in further reducing deaths from 2010 to 2050. Effectiveness of neuraminidase inhibitors in reducing illness and death, initially questioned whether it is a distinctly different boniva iv ...

Anti-Inflammatory, superinfection, epithelial, influenza, endosomal, conformational, Neuraminidase, Differentiation, inflammasome, pathogenic

In the last several years, public health officials have been monitoring two varieties of bird flu viruses with alarming properties: H7N9 and H5N8. Scientists at Emory have been probing the factors that limit reassortment between these strains and a well-known strain (H3N2) that has been dominating the last few flu seasons in the United States.. Helen Branswell has an article in STAT this week, explaining that H5N8 actually emerged from reassortment involving much-feared-but-not-damaging-to-humans-so-far H5N1:. Several years ago, these viruses effectively splintered, with some dumping their N1 neuraminidase - a gene that produces a key protein found on the surface of flu viruses - and replacing it with another. The process is called reassortment, and, in this case, it resulted in the emergence of a lot of new pairings over a fairly short period of time.. The most common and most dangerous viruses to emerge - for birds at least - have been H5N6 and H5N8 viruses. Both are highly pathogenic, meaning ...

Effect of different inhibitors on GR staining of γ/δ T cells treated with platelet supernatant fluid. Bovine lymphocytes were treated with neuraminidase (0.

Shop for Sculptresse by Panache Black Dana Strapless Bra at Next.co.uk. Next day delivery and free returns to store. 1000s of products online. Buy Sculptresse by Panache Black Dana Strapless Bra now!

investasi dana forex di- ets - investasi dana forex, monitoring forex broker, forex analyst report, trading system in forex, happy forex 1 5

UFC President Dana White talked about Ronda Rousey's impressive performance at UFC 190 on the post-fight show. White was all praise for Rousey's 34 second dismantling of Bethe Correia, and called her "the most badass woman anyone has ever seen." "You don't see women knock women out like that," White said. "She knocked her out. She's an absolute beast. She j

Creating a World of Change with Karlyn Emile 05, 11 Author: Dana Ratliff https://fiualumni.com/2016/07/27/creating-a-world-of-change-with-karlyn-emile-05-11/

Check out the UFC 216 Ultimate Media Day face-offs where UFC president Dana White was on guard, even though Tony Ferguson snuck it a little ...

At The Natural Path Center for Wellness we help our patients overcome and cope with a wide variety of health concerns. Below are some of the more common issues we assist people with ...

All of u - Stop answering questions. Instead ask me questions so I can answer. . All of u - ... | Page: 89 | 1630551 | Geet - Hui Sabse Parayee Forum

Direct OE replacement Jeep parts and accessories built to the original specifications by Omix-ADA. Limited five year manufacturers warranty.

We use cookies to ensure that we give you the best experience on our website. If you continue to use this site we will assume that you are happy with it.Ok ...