Man-specific, GalNAc/T/Tn-specific and Neu5Ac-specific seaweed lectins as glycan probes for the SARS-CoV-2 (COVID-19) coronavirus

Seaweed lectins, especially high-mannose-specific lectins from red algae, have been identified as potential antiviral agents that are capable of blocking the replication of various enveloped viruses like influenza virus, herpes virus, and HIV-1 in vitro. Their antiviral activity depends on the recognition of glycoprotein receptors on the surface of sensitive host cells—in particular, hemagglutinin for influenza virus or gp120 for HIV-1, which in turn triggers fusion events, allowing the entry of the viral genome into the cells and its subsequent replication. The diversity of glycans present on the S-glycoproteins forming the spikes covering the SARS-CoV-2 envelope, essentially complex type N-glycans and high-mannose type N-glycans, suggests that high-mannose-specific seaweed lectins are particularly well adapted as glycan probes for coronaviruses. This review presents a detailed study of the carbohydrate-binding specificity of high-mannose-specific seaweed lectins, demonstrating their potential to be used as specific glycan probes for coronaviruses, as well as the biomedical interest for both the detection and immobilization of SARS-CoV-2 to avoid shedding of the virus into the environment. The use of these seaweed lectins as replication blockers for SARS-CoV-2 is also discussed

Ancrage moléculaire des peptides dans la corbeille des groupes HLA-DQ2 et HLA-DQ8 : outil de prédiction des peptides immunotoxiques pour les malades cœliaques

International audienceCereal food products susceptible to generate immunotoxic peptides play a key role in the epidemiology of celiac disease and associated non IgE-mediated gluten intolerance disorders. The specific recognition by the basket of the HLA-DQ2 and HLA-DQ2 serotype groups of the corresponding immunotoxic peptides, triggers a cascade of molecular recognition events that lead to the inflammatory mechanisms responsible for the erosion of the villi covering the intestinal mucosa, currently observed in the severe forms of celiac disease. Accordingly, different in silico approaches have been proposed to predict the possible occurrence of immunotoxic peptides or immunotoxic-like peptides in food proteins of plant origin and, especially, of edible cereals, to prevent the consumption of deleterious food products by celiac disease suffering people. Among these approaches, the docking of putative imunotoxic-like peptides to the HLA-DQ2 and HLA-DQ8 basket consists of an interesting tool, especially when coupled to the bioinformatic research for amino acid sequence identities with genuine immunotoxic peptides from the gliadin and glutenin proteins already identified in gluten-containing cereals. However, the specificity of the DQ2- and DQ8-peptides has to be checked since some promiscuity has been observed among the immunotoxic peptides concerning their HLA-DQ2/HLA-DQ8-binding specificity. Docking experiments performed with a series of 26 genuine immunotoxic peptides from gluten-containing cereals (wheat, oat, barley, rye) were compared to the glutamine/proline-containing peptides from the non-gluten corn and rice cereals, for their HLA-DQ2/HLA-DQ8-binding capacity. None of the peptides from non-gluten cereals was able to completely bind the HLA-DQ2/HLA-DQ8 basket whereas all of the 26 genuine immunotoxic peptides from the gluten-containing cereals become adequately bound to the HLA-DQ basket, even though some promiscuity occurred between the DQ2- and DQ8-specific peptides. Docking to the HLA-DQ2/HLA-DQ8 serotypes thus consists of a relevant tool to predict the immunotoxic propensity of food proteins toward celiac disease suffering people, provided their sequence are known.Les céréales dont la protéolyse digestive est susceptible de générer des peptides immunotoxiques jouent un rôle déterminant dans l’épidémiologie de la maladie cœliaque et des intolérances sévères au gluten non IgE-médiées. La reconnaissance spécifique des peptides immunotoxiques par la corbeille des sérotypes HLA-DQ2 et HLA-DQ8 déclenche une cascade d’évènements moléculaires qui aboutit, par des mécanismes inflammatoires, à l’érosion des villosités de la muqueuse intestinale couramment observées dans les formes sévères de la maladie. Diverses approches prédictives in silico ont été proposées pour prédire l’existence de peptides immunotoxiques potentiels dans les protéines d’origine végétale, plus particulièrement des protéines de céréales, et éviter ainsi aux personnes souffrant de maladie cœliaque de consommer des aliments nocifs. Parmi ces approches, l’ancrage moléculaire (docking) des peptides candidats à la corbeille des sérotypes HLA-DQ2 et HLA-DQ8, constitue un outil prédictif intéressant surtout s’il est couplé à une recherche bioinformatique d’identités de séquence avec des peptides immunotoxiques de gliadines ou de glutélines connus. Cependant, la spécificité de reconnaissance des sérotypes DQ2 et DQ8 doit être prise en compte, en raison d’une certaine promiscuité qui permet aux sérotypes HALA-DQ2 de reconnaître des peptides DQ8 et, inversement, aux peptides HLA-DQ8 de reconnaître des peptides DQ2. L’ancrage moléculaire aux sérotypes HLA-DQ2 et HLA-DQ8 de 26 peptides immunotoxiques DQ2 et DQ8 issus de céréales à gluten (blé, orge, seigle, avoine) a été comparé à celui de peptides variés provenant de céréales dépourvues de gluten (maïs, riz). Aucun des peptides provenant de céréales sans gluten n’a été capable de s’ancrer correctement dans la corbeille des deux sérotypes tandis que tous les peptides provenant des céréales à gluten s’ancraient correctement malgré une certaine promiscuité observée dans l’ancrage des peptides DQ2 et DQ8. L’ancrage in silico des peptides candidats à la corbeille des sérotypes HLA-DQ2 et HLA-DQ8, constituent apparemment un outil intéressant pour prédire l’aptitude des protéines alimentaires à pouvoir libérer des peptides immunotoxiques par protéolyse digestive, sous réserve bien sûr, de pouvoir disposer de la séquence d’acides aminés des protéines à tester. Previous article in issu

Oléosomes: présence structure, allergénicité

International audienceOil bodies, or oleosomes, consist of lipid droplets confined within a protein-containing lipid monolayer that are widely distributed in oil seeds, particularly edible oil seeds. Amphiphilic proteins embedded in the lipid monolayer form an interface between the hydrophobic core of the oil bodies and the hydrophilic cytoplasm in which these organelles are distributed. They also play a crucial role in stabilizing oil bodies and preventing their coalescence via charge and steric hindrances. Oleosins, small proteins measuring 16–25 kDa, are the most abundant amphiphilic proteins occurring in the lipid monolayer surrounding the triglyceride core of oil bodies. They are composed of a hydrophobic α-helical hairpin anchored to the lipid monolayer and extended on both the N- and C-terminal ends by hydrophilic α-helical arms lying on the surface of the lipid monolayer in contact with the cytoplasm. Oleosins from peanut (Ara h 10, Ara h 11, Ara h 14, Ara h 15), hazelnut (Cor a 12, Cor a 13) and sesame (Ses i 4, Ses i 5) have been identified as major lipophilic IgE-binding allergens that are often associated with severe allergic reactions in sensitized subjects. Their allergenicity depends on the occurrence of IgE-binding epitopes along the hydrophilic arms attached to the hydrophobic α-helical hairpin. In addition, the phylogenetic relationships observed between oleosins belonging to different edible oil seeds suggest that some IgE-binding cross-reactivity may occur between oleosins of different origins. However, due to their lipophilic character, they are underrepresented in the water-soluble allergen extracts used in diagnosing food allergies and their role in triggering allergic responses in peanut and other tree nut allergies is thus doubtless greatly underestimated.Les oleosomes sont des organelles constitués d’une gouttelette lipidique limitée par une monocouche de lipides associée à des protéines, largement répandus dans les graines, notamment dans les graines des oléagineux alimentaires. Les protéines amphiphiles insérées dans la monocouche lipidique jouent un rôle d’interface entre le contenu lipidique hydrophobe des oléosomes et le cytoplasme essentiellement hydrophile dans lequel ils sont dispersés. Ils jouent également un rôle stabilisateur des oléosomes en s’opposant à leur coalescence dans le cytoplasme. Les oléosines, protéines amphiphiles de 16–25 kDa, sont les protéines les plus abondantes de la monocouche lipidique limitant les oléosomes. Elles sont constituées d’un cœur hydrophobe de deux hélices-α disposées en épingle à cheveu, qui pénètre jusque dans le contenu lipidique de l’oléosome au travers de la monocouche lipidique et assure ainsi l’ancrage de la protéine dans l’oléosome. Le cœur hydrophobe se prolonge par deux bras N- et C-terminaux de structure α-hélicoïdale, hydrophiles, qui s’étalent à la surface de l’oléosome, au contact du cytoplasme. Les oleosines de l’arachide (Ara h 10, Ara h 11, Ara h 14, Ara h 15), de la noisette (Cor a 12, Cor a 13) et du sésame (Ses i 4, Ses i 5), sont des allergènes lipophiles majeurs, impliqués en particulier dans des cas d’allergies alimentaires sévères. L’allergénicité des oléosines est liée à l’existence d’épitopes liant les IgE, situés sur les deux bras hydrophiles exposés à la surface des oléosomes. En outre, les affinités phylogénétiques existant entre les oléosines d’origine différente, suggèrent la possibilité d’une réactivité croisée, notamment entre plusieurs graines d’oléagineux alimentaires. Néanmoins, les oléosines sont pratiquement absentes des extrais allergéniques utilisés dans le diagnostic des allergies alimentaires, en raison de leur liposolubilité. En conséquence, leur potentiel allergénique est très probablement sous-estimé

Bases moleculaires de la réactivité croisée entre Act c 12 et les allergènes globulines 11S des graines : identification in silico des épitopes B d’Act c 12

International audienceKiwi fruit (Actinidia deliciosa, A. chinensis) is an important source of food allergy in children and adults in Western countries. The allergens responsible for this food allergy consist primarily of typical fruit allergens, e.g. the PR 10 Bet v 1-like allergen Act d 8, the cysteine protease actinidin Act d 1, the TLP Act d 2, and a chitinase. All of these allergens from A. deliciosa fruits have their counterparts in A. chinensis fruits. Recently, two other allergens belonging to the cupin superfamily (Act c 12) and the 2S albumin family (Act c 13), found in the kernels of A. chinensis fruit, have been identified as hidden fruit allergens responsible for IgE-binding cross-reactivity with peanuts and tree nuts. The sequential IgE-binding epitope regions of Act c 12 were predicted using a combination of in silico predictive approaches. Sequential IgE-binding epitopes of Act c 12 were predicted on a three-dimensional model of the protein from the amino acid sequence comparisons of the IgE-binding regions of cross-reacting cupins of peanuts and tree nuts. Residues of the sequence stretches exposed at the molecular surface were assigned as cross-reacting IgE-binding regions of Act c 12. In addition to their conformational similarities, these putative IgE-binding epitopes share a high degree of sequence similarity with the corresponding IgE-binding regions of peanut and tree-nut cupin allergens. The Act c 12 allergen offers an interesting example of a hidden fruit allergen likely to trigger allergic responses in individuals previously sensitized to peanut and other three-nut cupin allergens.(C) 2017 Elsevier Masson SAS. All rights reserved

Les grandes familles d’allergènes communes aux arthropodes (acariens, insectes, crustacés), mollusques et nématodes: réactions croisées et allergies croisées

International audienceAllergies to animal foods essentially result from the consumption of shellfish, including crustaceans and mollusks, and even edible insects traditionally eaten in different countries around the world. In all of these countries, the statistical data collected during the last decade point out the consumption of shellfish products as a likely cause of the most severe allergic reactions associated to animal-based foods. The allergens responsible for the shellfish allergies mainly consist of pan-allergens belonging to a limited number of protein families, widely distributed in mites, crustaceans, insects, mollusks and nematods. Major allergens are represented by muscle proteins (tropomyosin, troponin C, myosin, sarcoplasmic calcium-binding protein) and enzymes (α-amylase, arginine kinase, glutathione S-transferase, serine protease, triosephosphate isomerase), associated to other functional (hemocyanin, hexamerin) and structural (tubulin) proteins. Most of these pan-allergens exhibit quite well conserved amino acid sequences and readily superposable three-dimensional structures. Although they remain closely phylogenetically-related, they fall into distinct groups more or less distantly related within the phylogenetic trees, depending of the proteins. In this respect, insect tropomyosins fall into two separate groups closely related to mite and crustacean tropomyosin groups, respectively, whereas the mollusk tropomyosin group deviates from all other tropomyosin groups. Alpha-amylase and arginine kinase groups of insects and crustaceans remain closely related but are much more distant from the corresponding groups of mite, mollusk and nematod enzymes. Overall, allergens from insects and crustaceans feel closer whereas mollusks allergens clearly differ from all the other allergen groups. According to these phylogenetic relationships, the IgE-binding cross-reactivities frequently reported between these allergens of different origin could trigger some unexpected crossed allergic reactions in susceptible individuals. In this respect, the consumption of edible insects by shellfish allergic patients should be avoided.Les allergies alimentaires causées par les aliments d’origine animale proviennent essentiellement de la consommation de crustacés et de mollusques, voire d’insectes comestibles qui commencent à s’introduire sur le marché européen des produits alimentaires. Depuis plusieurs années, les statistiques établies par le CICBAA (centre d’investigations cliniques et biologiques en allergologie alimentaire) soulignent l’importance des crustacés et des mollusques dans la survenue de réactions systémiques sèvères liées à l’alimentation. L’allergénicité de ces aliments dépend de quelques familles d’allergènes communes aux arthropodes, aux mollusques et aux nématodes, qu’il est nécessaire de bien identifier pour diagnostiquer les allergies dont elles sont responsables. Ces allergènes correspondent à des protéines musculaires (tropomyosine, troponine C, myosine, actine, protéine sarcoplasmique fixant le calcium ou SCBP), des enzymes variées (α-amylase, arginine-kinase AK, glutathion S-transférase GST, trypsine, protéase à sérine, triosephosphate isomérase TPI) et des protéines circulantes (hemocyanine, hexamérine) ou structurales (tubulines). La plupart de ces protéines sont ubiquitaires et possèdent des séquences et surtout des structures très conservées et parfaitement superposables. Elles se répartissent dans les arbres phylogénétiques en groupes distincts dont les affinités restent élevées mais peuvent varier considérablement selon les allergènes. Ainsi, les tropomyosines des mollusques s’écartent nettement de celles des autres groupes et les tropomyosines d’insectes se répartissent en deux groupes dont un est proche des tropomyosines des acariens, l’autre des tropomyosines des crustacés. Les α-amylases et les arginine kinases des insectes et des crustacés sont très proches et toujours plus éloignées de celles des acariens, des mollusques et des nématodes. Globalement, les allergènes des insectes et des crustacés paraissent les plus proches tandis que les allergènes des mollusques s’écartent le plus des allergènes des autres groupes. L’existence, souvent rapportée, de réactions croisées entre ces différents groupes d’allergènes laisse présager des possibilités d’allergies croisées entre les acariens, les crustacés, les insectes, les mollusques et les nématodes. En particulier, le risque de réaction allergique associé à la consommation d’insectes comestibles (entomophagie) par des patients allergiques aux crustacés doit être envisagé

Les grandes familles d’allergènes communes aux arthropodes (acariens, insectes, crustacés), mollusques et nématodes: réactions croisées et allergies croisées

International audienceAllergies to animal foods essentially result from the consumption of shellfish, including crustaceans and mollusks, and even edible insects traditionally eaten in different countries around the world. In all of these countries, the statistical data collected during the last decade point out the consumption of shellfish products as a likely cause of the most severe allergic reactions associated to animal-based foods. The allergens responsible for the shellfish allergies mainly consist of pan-allergens belonging to a limited number of protein families, widely distributed in mites, crustaceans, insects, mollusks and nematods. Major allergens are represented by muscle proteins (tropomyosin, troponin C, myosin, sarcoplasmic calcium-binding protein) and enzymes (α-amylase, arginine kinase, glutathione S-transferase, serine protease, triosephosphate isomerase), associated to other functional (hemocyanin, hexamerin) and structural (tubulin) proteins. Most of these pan-allergens exhibit quite well conserved amino acid sequences and readily superposable three-dimensional structures. Although they remain closely phylogenetically-related, they fall into distinct groups more or less distantly related within the phylogenetic trees, depending of the proteins. In this respect, insect tropomyosins fall into two separate groups closely related to mite and crustacean tropomyosin groups, respectively, whereas the mollusk tropomyosin group deviates from all other tropomyosin groups. Alpha-amylase and arginine kinase groups of insects and crustaceans remain closely related but are much more distant from the corresponding groups of mite, mollusk and nematod enzymes. Overall, allergens from insects and crustaceans feel closer whereas mollusks allergens clearly differ from all the other allergen groups. According to these phylogenetic relationships, the IgE-binding cross-reactivities frequently reported between these allergens of different origin could trigger some unexpected crossed allergic reactions in susceptible individuals. In this respect, the consumption of edible insects by shellfish allergic patients should be avoided.Les allergies alimentaires causées par les aliments d’origine animale proviennent essentiellement de la consommation de crustacés et de mollusques, voire d’insectes comestibles qui commencent à s’introduire sur le marché européen des produits alimentaires. Depuis plusieurs années, les statistiques établies par le CICBAA (centre d’investigations cliniques et biologiques en allergologie alimentaire) soulignent l’importance des crustacés et des mollusques dans la survenue de réactions systémiques sèvères liées à l’alimentation. L’allergénicité de ces aliments dépend de quelques familles d’allergènes communes aux arthropodes, aux mollusques et aux nématodes, qu’il est nécessaire de bien identifier pour diagnostiquer les allergies dont elles sont responsables. Ces allergènes correspondent à des protéines musculaires (tropomyosine, troponine C, myosine, actine, protéine sarcoplasmique fixant le calcium ou SCBP), des enzymes variées (α-amylase, arginine-kinase AK, glutathion S-transférase GST, trypsine, protéase à sérine, triosephosphate isomérase TPI) et des protéines circulantes (hemocyanine, hexamérine) ou structurales (tubulines). La plupart de ces protéines sont ubiquitaires et possèdent des séquences et surtout des structures très conservées et parfaitement superposables. Elles se répartissent dans les arbres phylogénétiques en groupes distincts dont les affinités restent élevées mais peuvent varier considérablement selon les allergènes. Ainsi, les tropomyosines des mollusques s’écartent nettement de celles des autres groupes et les tropomyosines d’insectes se répartissent en deux groupes dont un est proche des tropomyosines des acariens, l’autre des tropomyosines des crustacés. Les α-amylases et les arginine kinases des insectes et des crustacés sont très proches et toujours plus éloignées de celles des acariens, des mollusques et des nématodes. Globalement, les allergènes des insectes et des crustacés paraissent les plus proches tandis que les allergènes des mollusques s’écartent le plus des allergènes des autres groupes. L’existence, souvent rapportée, de réactions croisées entre ces différents groupes d’allergènes laisse présager des possibilités d’allergies croisées entre les acariens, les crustacés, les insectes, les mollusques et les nématodes. En particulier, le risque de réaction allergique associé à la consommation d’insectes comestibles (entomophagie) par des patients allergiques aux crustacés doit être envisagé

Sécurité du maïs pour les patients souffrant de maladie cœliaque ?

International audienceMaize has long been recognized as a safe substitute for gluten-containing cereals for patients with severe gluten intolerance or celiac disease. Maize storage proteins consist primarily of zeins, which substantially differ from wheat gluten proteins, gliadins and glutenins. Yet sequence alignments reveal consistent identities and homologies between certain zeins and wheat gluten proteins. Systematic bioinfomatic searching for potential immunotoxic epitopes in all available amino acid sequences from maize storage proteins failed to identify any immunotoxic epitopes likely to provoke the intestinal mucosa erosion currently seen in celiac disease patients. The absence of immunotoxic epitopes in maize storage proteins was further confirmed by an in silico molecular docking approach, using HLA-DQ2 and HLA-DQ8 as templates. None of the suspected maize immunotoxic epitopes could be fully accommodated in the HCM-II basket of HLA-DQ2 and HLA-DQ8 during docking experiments. The results of the in silico approach confirm the absence of immunotoxic epitopes in maize storage proteins and help reinforce its status as a safe food for celiac disease patients. Maize thus deserves to be recognized as a gluten-free cereal with no harmful impact on celiac disease patients.Considéré comme un substitut fiable des céréales à gluten, le maïs fait encore l’objet de réserves concernant sa consommation par les patients souffrant d’intolérance sévère au gluten ou de maladie cœliaque. Les protéines de réserve des grains de maïs correspondent à des zéines, différentes des protéines du gluten de blé, gliadines et gluténines. Malgré tout, les alignements de séquence de certaines zéines montrent des homologies importantes avec les protéines du gluten de blé. Une recherche bio-informatique systématique des protéines de réserve du maïs disponibles, n’a cependant pas permis d’identifier dans ces protéines, des peptides immunotoxiques capables de provoquer l’érosion de la muqueuse intestinale. Ces peptides sont incapables de s’ancrer correctement dans la corbeille des groupes HLA-DQ2 et HLA-DQ8, comme le montrent les expériences d’ancrage moléculaire in silico. Ces peptides ne présentent donc aucun danger pour les patients souffrant d’intolérance sévère au gluten ou de maladie cœliaque. Le maïs est bien une céréale sans gluten qui peut être consommée sans danger par les patients souffrant de maladie cœliaque

Prédiction in silico de l'allergénicité des protéines

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Are Dietary Lectins Relevant Allergens in Plant Food Allergy?

International audienceLectins or carbohydrate-binding proteins are widely distributed in seeds and vegetative parts of edible plant species. A few lectins from different fruits and vegetables have been identified as potential food allergens, including wheat agglutinin, hevein (Hev b 6.02) from the rubber tree and chitinases containing a hevein domain from different fruits and vegetables. However, other well-known lectins from legumes have been demonstrated to behave as potential food allergens taking into account their ability to specifically bind IgE from allergic patients, trigger the degranulation of sensitized basophils, and to elicit interleukin secretion in sensitized people. These allergens include members from the different families of higher plant lectins, including legume lectins, type II ribosome-inactivating proteins (RIP-II), wheat germ agglutinin (WGA), jacalin-related lectins, GNA (Galanthus nivalis agglutinin)-like lectins, and Nictaba-related lectins. Most of these potentially active lectin allergens belong to the group of seed storage proteins (legume lectins), pathogenesis-related protein family PR-3 comprising hevein and class I, II, IV, V, VI, and VII chitinases containing a hevein domain, and type II ribosome-inactivating proteins containing a ricin B-chain domain (RIP-II). In the present review, we present an exhaustive survey of both the structural organization and structural features responsible for the allergenic potency of lectins, with special reference to lectins from dietary plant species/tissues consumed in Western countries

A Proteomic- and Bioinformatic-Based Identification of Specific Allergens from Edible Insects: Probes for Future Detection as Food Ingredients

International audienceThe increasing development of edible insect flours as alternative sources of proteins added to food and feed products for improving their nutritional value, necessitates an accurate evaluation of their possible adverse side-effects, especially for individuals suffering from food allergies. Using a proteomic- and bioinformatic-based approach, the diversity of proteins occurring in currently consumed edible insects such as silkworm (Bombyx mori), cricket (Acheta domesticus), African migratory locust (Locusta migratoria), yellow mealworm (Tenebrio molitor), red palm weevil (Rhynchophorus ferrugineus), and giant milworm beetle (Zophobas atratus), was investigated. Most of them consist of phylogenetically-related protein allergens widely distributed in the different groups of arthropods (mites, insects, crustaceans) and mollusks. However, a few proteins belonging to discrete protein families including the chemosensory protein, hexamerin, and the odorant-binding protein, emerged as proteins highly specific for edible insects. To a lesser extent, other proteins such as apolipophorin III, the larval cuticle protein, and the receptor for activated protein kinase, also exhibited a rather good specificity for edible insects. These proteins, that are apparently missing or much less represented in other groups of arthropods, mollusks and nematods, share well conserved amino acid sequences and very similar three-dimensional structures. Owing to their ability to trigger allergic responses in sensitized people, they should be used as probes for the specific detection of insect proteins as food ingredients in various food products and thus, to assess their food safety, especially for people allergic to edible insects