Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “NEURAMINIDASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed1993

Characterization of neuraminidases produced by various serotypes of Pasteurella haemolytica.

Neuraminidases produced by 16 strains of Pasteurella haemolytica (serotypes 1 to 16) were characterized by molecular weight, antigenic identity, and substrate specificity. After growth in a chemically defined medium, stage I (lyophilized) culture supernatants were assayed for activity with N-acetylneuramin lactose, human alpha-1-acid glycoprotein, fetuin, colominic acid, and bovine submaxillary mucin. Neuraminidase produced by P. haemolytica serotype A1 (Ph A1) was purified by a combination of salt fractionation, ion-exchange chromatography on DEAE-Sephacel, and gel filtration on Sephadex G-200. Purified Ph A1 neuraminidase was used to immunize rabbits, and the resultant antiserum reduced the activity of Ph A1 neuraminidase by 46%. This antiserum also reduced the activity of neuraminidase produced by the other serotypes by between 15 and 66%. Molecular weight estimates of the neuraminidases produced by the various serotypes were obtained by gel filtration chromatography on Sephadex G-200. Fifteen of the 16 serotypes examined produced a neuraminidase with a molecular weight of approximately 150,000 to 200,000. One serotype (serotype 11) produced no material with neuraminidase activity. In addition, all 15 high-molecular-weight neuraminidases showed similar substrate specificities. That is, they were all most active against N-acetylneuramin lactose and least active against bovine submaxillary mucin. On the basis of these results, it appears that the high-molecular-weight neuraminidases produced by the different P. haemolytica serotypes are quite similar.

Mannheimia haemolytica↗
PubMed1988

Variation of leukocyte neuraminidase with Duke stage in patients with adenocarcinoma of the colon and rectum.

In 14 patients with adenocarcinoma of the colon or rectum (Duke stages A to D), positive results for neuraminidase were obtained with the isolated leukocytes at pH 6. These were tested by a cytochemical method using a chromogenic substrate for neuraminidase. Under the same conditions, normal leukocyte neuraminidase has a pH optimum of 4. The percentage of leukocytes showing neuraminidase activity increased with the progression of Duke stage and presence of liver or peritoneal metastases. Neuraminidase activity was also found in tumor and metastases specimens of these patients as well as in a human cell line derived from colonic adenocarcinoma (HT-29). Neuraminidase antibodies were found in blood and certain tumor materials. Neuraminidase inhibition tests were positive with neuraminidase inhibitors, patients' sera, N2 neuraminidase antibodies, and antisera against some type C retroviruses (GaLV and MLV), which were used because highly purified MLV preparations proved to contain biologically active neuraminidase (N2).

Adenocarcinoma↗
PubMed1995

Structural and functional-group tuning in the design of neuraminidase inhibitors.

Analogues of the disaccharide alpha-NeuAc-(2-->6)-beta-D-Gal-OR have been made by modifications at C-1 and C-6 of the galactose and at C-4 of the NeuAc unit, for structure-activity relationship studies with influenza virus neuraminidase. These studies indicate that for the influenza neuraminidase, a larger aglycon at C-1 of galactose is less preferred, whereas the restriction of the rotamer orientation at C-6 of galactose in the "tg" mode favors enzyme binding. Substitution at C-4 of the NeuAc unit has the most profound effect in the influenza neuraminidase hydrolysis and inhibition. For example, azido and acetamido groups at C-4 of the NeuAc units render the sialosides resistant to neuraminidase hydrolysis. However, these derivatives are not inhibitors of the neuraminidase, indicating their lack of binding. On the other hand, a 4-amino substitution of the NeuAc unit not only renders the corresponding sialosides neuraminidase-resistant, but also makes them potent neuraminidase inhibitors. This potent inhibition indicates that the 4-amino groups in these sialosides may engage in favorable interaction with amino acids at the neuraminidase active-site. The conclusion is also supported by docking studies of the carbohydrate structures at the neuraminidase active-site.

Amino Sugars↗
PubMed1986

Renal neuraminidase. Characterization in normal rat kidney and measurement in experimentally induced nephrotic syndrome.

Several lines of evidence suggest that increased neuraminidase activity may be responsible for the loss of glomerular N-acetylneuraminic acid (AcNeu) observed in various glomerular diseases. However, virtually no information is available on the activity of neuraminidase in glomeruli or the potential role of this enzyme in glomerular pathophysiology. Utilizing 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (4MU-AcNeu) as substrate, we defined optimal assay conditions and characterized neuraminidase activity in glomeruli and, for comparison, in other renal fractions and liver. Neuraminidase activity in glomeruli, cortex and tubules was maximal at pH 4.4. The Km for 4MU-AcNeu was estimated to be 195 microM for glomeruli and 226 microM for cortex. Glomerular neuraminidase was inhibited by AcNeu (90% at 25 mM) and high concentrations of Triton X-100 (26% at 0.5%), but unaffected by CaCl2, EDTA or N-ethylmaleimide (each 1 mM). Neuraminidase activity (nmol/h per mg of protein; mean +/- S.E.M.) in normal rat kidney was: cortex, 14.47 +/- 0.76; medulla, 7.85 +/- 0.64; papilla, 2.64 +/- 0.11; tubules, 13.79 +/- 0.70; glomeruli, 5.57 +/- 0.28. In comparison, neuraminidase activity in rat liver was 2.58 +/- 0.14. Puromycin aminonucleoside (PAN)-induced nephrotic syndrome is a model of glomerular disease in which the loss of glomerular AcNeu is well documented. In two separate studies, we observed no change in the specific activity of neuraminidase in either glomeruli or cortex isolated from rats treated with PAN (15 mg/100 g, intraperitoneally) and killed at either the onset or the peak of proteinuria. Results were similar whether neuraminidase activity was expressed per mg of protein or per microgram of DNA.

Animals↗
PubMed2000

Lysosomal neuraminidase. Catalytic activation in insect cells is controlled by the protective protein/cathepsin A.

Lysosomal N-Acetyl-alpha-neuraminidase is active in complex with the protective protein/cathepsin A (PPCA) and beta-galactosidase. The interaction with PPCA is essential for the correct intracellular routing and lysosomal localization of neuraminidase, but the mechanism of its catalytic activation is unclear. To investigate this process, we have used the baculovirus expression system to co-express neuraminidase and PPCA precursors in insect cells, which resulted in high enzymatic activity of neuraminidase. Both the 34- and 20-kDa PPCA subunits were required for the activation. We further demonstrated that when expressed alone, the neuraminidase precursor remained dimeric (114 kDa) and had low enzymatic activity, but when co-expressed with PPCA and beta-galactosidase, it multimerized in a complex of approximately 1350 kDa, together with the other two proteins. The fully active neuraminidase co-precipitated with full-length PPCA and beta-galactosidase precursors. However, when co-expressed with the individual PPCA subunits, neuraminidase co-precipitated only with the small 20-kDa polypeptide, which therefore must contain a neuraminidase-binding site. Our finding suggests a model of activation of neuraminidase dependent on its oligomerization at acidic pH that is mediated by interaction with PPCA.

Animals↗
PubMed1981

Neuraminidase production by Bacteroidaceae.

The production of neuraminidase (EC 3.2.1.18) by 77 strains of Bacteroidaceae was investigated by techniques previously used to study neuraminidase production by clostridia. Conditions for culture and assay of Bacteroides fragilis neuraminidase were characterised. The enzyme is predominantly cell associated; it is not calcium dependent and the pH optimum for its production is c. 4.5. Most neuraminidase-positive Bacteroides strains produced the enzyme well in the test media but a few strains failed to produce it consistently in one or other of the media. Because of these occasional variations, strains were grown and tested in at least two media before being defined as neuraminidase negative. Within the B. fragilis group of species, B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron and B. variabilis were neuraminidase positive while B. eggerthii, B. uniformis and B. splanchnicus were negative. Two subspecies of B. melaninogenicus (ss. melaninogenicus and ss. levii) were positive but the other (ss. intermedius) was negative. Strains of B. oralis and B. bivius produced the enzyme while B. ruminicola, B. disiens, B. asaccharolyticus and B. corrodens did not. The microaerophilic B. ochraceus were also positive. None of the Fusobacterium or Leptotrichia species tested produced neuraminidase. Our results for neuraminidase production are consistent for all strains of each species examined and we suggest that tests for neuraminidase production would be a valuable addition to biochemical tests currently used in taxonomic studies of the Bacteroidaceae.

Bacteroidaceae↗
PubMed1987

Characterization of neuraminidases produced by various serotypes of group B streptococci.

Neuraminidase produced by 11 strains of group B streptococci (GBS), from serotypes Ia, Ib, Ic, II, and III, were characterized according to molecular weight, antigenic identity, and substrate specificity. Following growth in a chemically defined medium, ammonium sulfate-concentrated culture supernatants were assayed for activity with bovine submaxillary mucin as substrate. Neuraminidase produced by GBS strain 122 (serotype III) was purified by a combination of salt fractionation, affinity chromatography with Affi-Gel Blue, ion-exchange chromatography with DEAE-cellulose, and gel filtration on Sephadex G-200. Purified neuraminidase was used to immunize rabbits, and the resultant antiserum reduced the activity of purified neuraminidase from strain 122 by 87.7%. The antiserum also reduced the activity of neuraminidases produced by the other four serotypes by between 78.3 and 90%. Molecular weight estimates of the neuraminidases produced by the various serotypes were obtained by gel filtration chromatography on Sephadex G-200. The molecular weights obtained for the neuraminidases from the representative strains of each serotype ranged from 110,000 to 180,000. In addition, all of the GBS neuraminidases examined (regardless of the producing serotype) were active only on bovine submaxillary mucin. On the basis of these results, it appears that the neuraminidases produced by different GBS serotypes are quite similar.

Antibodies, Bacterial↗
PubMed2006

Bacterial neuraminidase facilitates mucosal infection by participating in biofilm production.

Many respiratory pathogens, including Hemophilus influenzae, Streptococcus pneumoniae, and Pseudomonas aeruginosa, express neuraminidases that can cleave alpha2,3-linked sialic acids from glycoconjugates. As mucosal surfaces are heavily sialylated, neuraminidases have been thought to modify epithelial cells by exposing potential bacterial receptors. However, in contrast to neuraminidase produced by the influenza virus, a role for bacterial neuraminidase in pathogenesis has not yet been clearly established. We constructed a mutant of P. aeruginosa PAO1 by deleting the PA2794 neuraminidase locus (Delta2794) and tested its virulence and immunostimulatory capabilities in a mouse model of infection. Although fully virulent when introduced i.p., the Delta2794 mutant was unable to establish respiratory infection by i.n. inoculation. The inability to colonize the respiratory tract correlated with diminished production of biofilm, as assessed by scanning electron microscopy and in vitro assays. The importance of neuraminidase in biofilm production was further demonstrated by showing that viral neuraminidase inhibitors in clinical use blocked P. aeruginosa biofilm production in vitro as well. The P. aeruginosa neuraminidase has a key role in the initial stages of pulmonary infection by targeting bacterial glycoconjugates and contributing to the formation of biofilm. Inhibiting bacterial neuraminidases could provide a novel mechanism to prevent bacterial pneumonia.

Amino Acid Sequence↗
PubMed1985

Effects of neuraminidase on lectin binding sites in photoreceptor cells of monkey retina.

Binding of sugar-specific lectins to the monkey retina was investigated with particular reference to the effects of pretreatment with neuraminidase on the photoreceptor cells. Neuraminidase-treated or untreated retinal sections were examined with a fluorescence microscope after incubation with the following fluorescein-labeled lectins: peanut agglutinin (PNA), wheat germ agglutinin (WGA), Ricinus communis agglutinin-1 (RCA-1) and Dolichos biflorus agglutinin (DBA). In the neuraminidase-untreated tissue, PNA, which is specific for D-galactose beta 1----3 N-acetyl-D-galactosamine (Gal beta 1----3GalNAc), was bound preferentially to the cones, and after treatment of sections with neuraminidase, PNA could bind to both cones and rods. WGA, which is specific for sialic acid and N-acetyl-D-glucosamine, was strongly bound to the rods but moderately to the cones without neuraminidase pretreatment, whereas neuraminidase-treated sections showed a weak binding. RCA-1, which is specific for D-galactose, showed patchy fluorescence on the basal and distal portions of the outer segments of the cones and rods, whereas neuraminidase-treated sections had uniform fluorescence throughout the tissues. DBA, which is specific for N-acetyl-D-galactosamine, did not bind to either cones or rods before and after neuraminidase treatment. These results suggest that there is a difference in the carbohydrate chains of glycoconjugates in the cones and rods: in the cones Gal beta 1----3GalNAc may be the terminal sugar as recognized by PNA, whereas in the rods this sugar is contained in the carbohydrate chain but masked by terminal sialyl residues so that those glycoconjugates are inaccessible to PNA without neuraminidase treatment.

Animals↗
PubMed1995

Phospholipase C-mediated release of neuraminidase from Tritrichomonas foetus cell surface.

The release of the Tritrichomonas foetus plasma-membrane ectoenzyme neuraminidase by exogenous specific phospholipase C (PI-PLC) was investigated. Neuraminidase activity was determined using both the peanut agglutinin (PNA) hemagglutination test and the specific substrate N-acetylneuramin-lactose in a colorimetric assay. The release of the neuraminidase by PI-PLC was dependent on the reaction time and the concentration of PI-PLC. Neuraminidase activity was also detected in supernatant of untreated T. foetus. Spontaneous or PI-PLC-induced release of neuraminidase from protozoan cells was markedly decreased by 10 mM ZnCl2, suggesting the occurrence of an endogenous PI-PLC in the parasite. After T. foetus lysis at 37 degrees C with a solution of Triton X-114, neuraminidase activity was preferentially found in the aqueous phase rather than in the detergent phase, again suggesting that the parasite contains an endogenous PI-PLC that converts the hydrophobic form of neuraminidase anchored to the T. foetus cell membrane into a hydrophilic form. These results show that neuraminidase is linked to the T. foetus plasma membrane via a glycosylphosphatidylinositol anchor.

Animals↗
PubMed1977

Neuraminidase and tumor immunotherapy.

Preliminary results of first clinical studies with the enzyme neuraminidase call attention to a new kind of cancer treatment. This promising approach to tumor immunotherapy was entered into the clinical phase as a consequence of successful experimental studies in tumor-bearing mice, rats and dogs. In this review, the presently known and essential results of experimental and clinical studies on tumor immunotherapy by means of neuraminidase are presented as well as some necessary and critical considerations in this context. Moreover, out of a broad variety of results of biochemical and biological in vitro studies, it was attempted to select the more essential knowledge which could contribute to a better understanding of the still rather unclear in vivo mode of action of the enzyme neuraminidase. In a first brief paragraph (1.0), the biochemically characteristic data of the enzyme neuraminidase is presented. In the second section (2.0), the basic knowledge about the effects of neuraminidase on cell behavior is rather amply contained. Here, on the one hand, the biophysical and biochemical alterations are mentioned, the so-called ""unmasking'' effects are reconsidered and, on the other hand, the effects on the immunologically responding cell are discussed. In a third section (3.0), the diverse findings from animal experiments using neuraminidase-treated tumor cells are confronted, whereby tumor transplantation experiments and tumor therapy experiments are dealt with separately. The last section (4.0) reports about the first clinical studies with neuraminidase-treated autologous as well as homologous tumor cells, which partly brought about rather surprising and astonishing success. On the basis of recent findings by the study group of the authors, the more prior and sometimes discrepant results of various groups are critically considered. The problems of alteration of antigenicity and of other properties of cells through splitting off membrane-bound neuraminic acid, the facts of adjuvanticity of neuraminidase itself, the relation of successful therapy to dose dependency as well as the relation of undesirable methods for tumor mass reduction to the immunological responsiveness of the tumor bearer were especially looked into.

Animals↗
PubMed1990

Measurement of anti-influenza neuraminidase antibody using a peroxidase-linked lectin and microtitre plates coated with natural substrates.

Neuraminidase-induced removal of sialic acid from natural substrates (desialylation) unmasks saccharides that are specifically recognized by the lectin peanut agglutinin (PNA). We demonstrate that, when a neuraminidase substrate is coated on to the wells of a microplate, it is possible to quantitate the binding of PNA to the desialylated substrate using a peroxidase-conjugated PNA (Po-PNA). The amount of bound PNA correlated directly with the amount of sialic acid removed from the substrate and therefore with the neuraminidase activity. By reacting with specific epitopes that are located near to the enzyme active site, anti-neuraminidase antibodies are capable of inhibiting the virus-induced desialylation of the substrate. Such antibodies therefore reduce the binding of Po-PNA. The advantage of this assay is that since different natural substrates for neuraminidase (erythrocytes, fetuin or gangliosides) can be used to coat the microplates, the capacity of anti-neuraminidase antibody to inhibit the neuraminidase activity towards different types of sialoglycoconjugates can be evaluated. Anti-hemagglutinin or non-specific anti-neuraminidase antibody have no interfering reactivity.

Animals↗
PubMed1991

Effects of neuraminidase on cellular calcium and contraction in cultured cardiac myocytes.

Mammalian plasma membranes, including the myocardial sarcolemma, are abundantly glycosylated. Sialic acid is a ubiquitous anionic sugar found at the periphery of sarcolemmal glycoconjugates. The physiological role of this sugar is not clear, but neuraminidase, which specifically hydrolyzes sialic acid from the sarcolemma, has been found to increase calcium exchange, cause electrophysiological abnormalities, and enhance the transient (T) calcium current in cardiac myocytes. The purpose of this study was to better characterize the effect of neuraminidase on cellular calcium (Ca) and contractile function. Neuraminidase removed up to 57% of total sialic acid from the cells. 45Ca exchange was measured and neuraminidase was found to increase cell calcium proportional to the amount of sialic acid removed (18.6 +/- 0.8 mmol/kg dry w, maximally). Over 80% of the increment in calcium remained rapidly exchangeable (t1/2 less than 15 s) under non-perfusion limited conditions and was inhibited by cations (La greater than Cd greater than Mn greater than Mg) and nifedipine. Using a video-monitoring system, neuraminidase was observed to transiently increase cell shortening during contraction (30 +/- 9%), with progression to arrhythmias followed by cessation of contraction. These results indicate that neuraminidase, probably by removing sarcolemmal sialic acid residues, greatly augments cellular calcium in cultured cardiac myocytes. Most of the increment in Ca induced by neuraminidase was very rapidly exchangeable and most likely mediated by a Ca specific mechanism. Additionally, neuraminidase treatment altered contractile function in a manner consistent with elevated cellular Ca. Despite the many-fold increase in cellular Ca induced by sialic acid removal, cells recovered and demonstrated rhythmic contractions upon return to control incubation conditions.

Animals↗
PubMed1992

Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex.

The crystal structure of the complex between neuraminidase from influenza virus (subtype N9 and isolated from an avian source) and the antigen-binding fragment (Fab) of monoclonal antibody NC41 has been refined by both least-squares and simulated annealing methods to an R-factor of 0.191 using 31,846 diffraction data in the resolution range 8.0 to 2.5 A. The resulting model has a root-mean-square deviation from ideal bond-length of 0.016 A. One fourth of the tetrameric complex comprises the crystallographic model, which has 6577 non-hydrogen atoms and consists of 389 protein residues and eight carbohydrate residues in the neuraminidase, 214 residues in the Fab light chain, and 221 residues in the heavy chain. One putative Ca ion buried in the neuraminidase, and 73 water molecules, are also included. A remarkable shape complementarity exists between the interacting surfaces of the antigen and the antibody, although the packing density of atoms at the interface is somewhat looser than in the interior of a protein. Similarly, there is a high degree of chemical complementarity between the antigen and antibody, mediated by one buried salt-link, two solvated salt-links and 12 hydrogen bonds. The antibody-binding site on neuraminidase is discontinuous and comprises five chain segments and 19 residues in contact, whilst 33 neuraminidase residues in eight segments have 899 A2 of surface area buried by the interaction (to a 1.7 A probe), including two hexose units. Seventeen residues in NC41 Fab lying in five of the six complementarity determining regions (CDRs) make contact with the neuraminidase and 36 antibody residues in seven segments have 916 A2 of buried surface area. The interface is more extensive than those of the three lysozyme-Fab complexes whose crystal structures have been determined, as judged by buried surface area and numbers of contact residues. There are only small differences (less than 1.5 A) between the complexed and uncomplexed neuraminidase structures and, at this resolution and accuracy, those differences are not unequivocal. The main-chain conformations of five of the CDRs follow the predicted canonical structures. The interface between the variable domains of the light and heavy chains is not as extensive as in other Fabs, due to less CDR-CDR interaction in NC41. The first CDR on the NC41 Fab light chain is positioned so that it could sterically hinder the approach of small as well as large substrates to the neuraminidase active-site pocket, suggesting a possible mechanism for the observed inhibition of enzyme activity by the antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed2005

Sensitivity of influenza viruses to zanamivir and oseltamivir: a study performed on viruses circulating in France prior to the introduction of neuraminidase inhibitors in clinical practice.

Influenza virus neuraminidase inhibitors (NAIs) were introduced in clinical practice in various parts of the world since 1999 but were only scarcely distributed in France. Prior to the generalization of zanamivir and oseltamivir utilization in our country, we decided to test a large panel of influenza strains to establish the baseline sensitivity of these viruses to anti-neuraminidase drugs, based upon a fluorometric neuraminidase enzymatic test. Our study was performed on clinical samples collected by practitioners of the GROG network (Groupe Régional d'Observation de la Grippe) in the south of France during the 2002-2003 influenza season. Out of 355 isolates tested in the fluorometric neuraminidase activity assay, 267 isolates could be included in inhibition assay against anti-neuraminidase drugs. Differences in IC50 range were found according to the subtype and the anti-neuraminidase drug. Influenza B and A/H1N1 viruses appeared to be more sensitive to zanamivir than to oseltamivir (mean B IC50 values: 4.19 nM versus 13 nM; mean H1N1 IC50 values: 0.92 nM versus 1.34 nM), while A/H1N2 and A/H3N2 viruses were more sensitive to oseltamivir than to zanamivir (mean H3N2 IC50 values: 0.67 nM versus 2.28 nM; mean H1N2 IC50 values: 0.9 nM versus 3.09 nM). Out of 128 N2 carrying isolates, 10 isolates had zanamivir or oseltamivir IC50 values in upper limits compared to their respective data range. Sequencing of the neuraminidase of these outliers N2 highlighted several mutations, but none of them were associated with resistance to neuraminidase inhibitors.

Acetamides↗
PubMed2005

Neuraminidase production by Erysipelothrix rhusiopathiae.

In order to characterise neuraminidase activity by Erysipelothrix, 85 isolates of Erysipelothrix spp. from a variety of sources including human clinical, marine and terrestrial animals, and the environment were investigated for neuraminidase production. Neuraminidase activity was detected by a peanut lectin haemagglutination method. The effects of media, incubation conditions and pH on the production and activity of neuraminidase were also investigated. Enzyme activity was detected only in the supernatants of the isolates of Erysipelothrix rhusiopathiae which had been incubated in cooked meat broth and Todd Hewitt broth supplemented with horse serum after 16 and 36 h incubation at 37 degrees C. The maximum titres were reached at 40 h in cooked meat broth and 56 h in Todd Hewitt broth supplemented with horse serum. All 58 isolates and the type strain (ATCC 19414) of E. rhusiopathiae produced detectable neuraminidase activity with titres between 10 and 320. The optimal pH for the enzyme activity varied among the isolates with a pH between 6.0 and 7.0 covering the highest enzyme activity of the most. There was no statistically significant difference in the level of neuraminidase activity between isolates from different sources (p > 0.05). Neuraminidase activity was not detected in the non-pathogenic Erysipelothrix spp. such as E. tonsillarum. Neuraminidase was detected only in E. rhusiopathiae suggesting its possible role as a virulence factor. Enzyme production and activity were medium and pH dependent. The peanut lectin haemagglutination assay is a simple, rapid and sensitive method and is particularly useful for the analysis of multiple samples.

Animals↗
PubMed1977

Influenza A neuraminidase antibodies in children and young adults studied by serum absorption.

A study is described of influenza A anti-neuraminidase antibodies in the sera of young people of three different groups. Each serum was individually absorbed with viruses containing the N2 neuraminidases of 1957, 1968 and 1972. Rabbit antisera prepared against the viruses were similarly absorbed. Results obtained with the animal sera suggested that these neuraminidases were antigenically distinct, but the human sera had a broader range of anti-neuraminidase activity and gave indication of asymmetric antigenic relationships. Earlier workers who surveyed anti-haemagglutinin antibodies reported that the virus of primary infection absorbed all antibodies, and the virus of secondary infection only those directed against itself. We too found that the virus of secondary infection absorbed only homologous anti-neuraminidase antibody. However, although the primary infecting virus did absorb some secondary antibody, this absorption was incomplete and it lessened with the lengthening of the time interval between the primary and secondary infecting viruses. A similar pattern was seen with anti-haemagglutinin antibodies. Absorption of anti-neuraminidase antibodies from human sera proved much more difficult than absorption of anti-haemagglutinin antibodies particularly after repeated influenza virus infections. The relative rarity of antigenic shift in the neuraminidase subunit also creates problems in the interpretation of results of serum neuraminidase antibody surveys.

Adult↗
PubMed1998

Structure-activity relationship studies of novel carbocyclic influenza neuraminidase inhibitors.

A series of influenza neuraminidase inhibitors with the cyclohexene scaffold containing lipophilic side chains have been synthesized and evaluated for influenza A and B neuraminidase inhibitory activity. The size and geometry of side chains have been modified systematically in order to investigate structure-activity relationships of this class of compounds. The X-ray crystal structures of several analogues complexed with neuraminidase revealed that the lipophilic side chains bound to the hydrophobic pocket consisted of Glu276, Ala246, Arg224, and Ile222 of the enzyme active site. The structure-activity relationship studies of this series have also demonstrated remarkably different inhibitory potency between influenza A and B neuraminidase. This indicated that the lipophilic side chains had quite different hydrophobic interactions with influenza A and B neuraminidase despite their complete homology in the active site. Influenza B neuraminidase appeared to be much more sensitive toward the increased steric bulkiness of inhibitors compared to influenza A neuraminidase. From the extensive structure-activity relationship investigation reported in this article, GS 4071 emerged as one of the most potent influenza neuraminidase inhibitors against both influenza A and B strains.

Acetamides↗