scholarly journals Mannose-Specific Lectins from Marine Algae: Diverse Structural Scaffolds Associated to Common Virucidal and Anti-Cancer Properties

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 440 ◽  
Author(s):  
Annick Barre ◽  
Mathias Simplicien ◽  
Hervé Benoist ◽  
Els J.M. Van Damme ◽  
Pierre Rougé
Keyword(s):  
Diagnostic Tools ◽  
Carbohydrate Binding ◽  
Legume Lectin ◽  
Therapeutic Drugs ◽  
Anti Cancer ◽  
Glycoprotein Gp120 ◽  
Lectin Family ◽  
High Mannose ◽  
Hiv 1

To date, a number of mannose-specific lectins have been isolated and characterized from seaweeds, especially from red algae. In fact, man-specific seaweed lectins consist of different structural scaffolds harboring a single or a few carbohydrate-binding sites which specifically recognize mannose-containing glycans. Depending on the structural scaffold, man-specific seaweed lectins belong to five distinct structurally-related lectin families, namely (1) the griffithsin lectin family (β-prism I scaffold); (2) the Oscillatoria agardhii agglutinin homolog (OAAH) lectin family (β-barrel scaffold); (3) the legume lectin-like lectin family (β-sandwich scaffold); (4) the Galanthus nivalis agglutinin (GNA)-like lectin family (β-prism II scaffold); and, (5) the MFP2-like lectin family (MFP2-like scaffold). Another algal lectin from Ulva pertusa, has been inferred to the methanol dehydrogenase related lectin family, because it displays a rather different GlcNAc-specificity. In spite of these structural discrepancies, all members from the five lectin families share a common ability to specifically recognize man-containing glycans and, especially, high-mannose type glycans. Because of their mannose-binding specificity, these lectins have been used as valuable tools for deciphering and characterizing the complex mannose-containing glycans from the glycocalyx covering both normal and transformed cells, and as diagnostic tools and therapeutic drugs that specifically recognize the altered high-mannose N-glycans occurring at the surface of various cancer cells. In addition to these anti-cancer properties, man-specific seaweed lectins have been widely used as potent human immunodeficiency virus (HIV-1)-inactivating proteins, due to their capacity to specifically interact with the envelope glycoprotein gp120 and prevent the virion infectivity of HIV-1 towards the host CD4+ T-lymphocyte cells in vitro.

scholarly journals Man-Specific, GalNAc/T/Tn-Specific and Neu5Ac-Specific Seaweed Lectins as Glycan Probes for the SARS-CoV-2 (COVID-19) Coronavirus

Marine Drugs ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. 543
Author(s):  
Annick Barre ◽  
Els J.M. Van Damme ◽  
Mathias Simplicien ◽  
Hervé Benoist ◽  
Pierre Rougé
Keyword(s):  
Influenza Virus ◽  
Antiviral Agents ◽  
Host Cells ◽  
Carbohydrate Binding ◽  
Complex Type ◽  
Enveloped Viruses ◽  
High Mannose ◽  
Hiv 1 ◽  
Biomedical Interest

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.

scholarly journals High Mannose-binding Lectin with Preference for the Cluster of α1–2-Mannose from the Green Alga Boodlea coacta Is a Potent Entry Inhibitor of HIV-1 and Influenza Viruses

2011 ◽  
Vol 286 (22) ◽  
pp. 19446-19458 ◽  
Author(s):  
Yuichiro Sato ◽  
Makoto Hirayama ◽  
Kinjiro Morimoto ◽  
Naoki Yamamoto ◽  
Satomi Okuyama ◽  
...  
Keyword(s):  
Green Alga ◽  
Influenza Viruses ◽  
Viral Envelope ◽  
Host Cells ◽  
Carbohydrate Binding ◽  
Sequence Motif ◽  
High Association ◽  
High Mannose ◽  
Hiv 1 ◽  
Boodlea Coacta

The complete amino acid sequence of a lectin from the green alga Boodlea coacta (BCA), which was determined by a combination of Edman degradation of its peptide fragments and cDNA cloning, revealed the following: 1) B. coacta used a noncanonical genetic code (where TAA and TAG codons encode glutamine rather than a translation termination), and 2) BCA consisted of three internal tandem-repeated domains, each of which contains the sequence motif similar to the carbohydrate-binding site of Galanthus nivalis agglutinin-related lectins. Carbohydrate binding specificity of BCA was examined by a centrifugal ultrafiltration-HPLC assay using 42 pyridylaminated oligosaccharides. BCA bound to high mannose-type N-glycans but not to the complex-type, hybrid-type core structure of N-glycans or oligosaccharides from glycolipids. This lectin had exclusive specificity for α1–2-linked mannose at the nonreducing terminus. The binding activity was enhanced as the number of terminal α1–2-linked mannose substitutions increased. Mannobiose, mannotriose, and mannopentaose were incapable of binding to BCA. Thus, BCA preferentially recognized the nonreducing terminal α1–2-mannose cluster as a primary target. As predicted from carbohydrate-binding propensity, this lectin inhibited the HIV-1 entry into the host cells at a half-maximal effective concentration of 8.2 nm. A high association constant (3.71 × 108m−1) of BCA with the HIV envelope glycoprotein gp120 was demonstrated by surface plasmon resonance analysis. Moreover, BCA showed the potent anti-influenza activity by directly binding to viral envelope hemagglutinin against various strains, including a clinical isolate of pandemic H1N1-2009 virus, revealing its potential as an antiviral reagent.

scholarly journals Identification of a CD36-related Thrombospondin 1–binding Domain in HIV-1 Envelope Glycoprotein gp120: Relationship to HIV-1–specific Inhibitory Factors in Human Saliva

1998 ◽  
Vol 187 (1) ◽  
pp. 25-35 ◽  
Author(s):  
René Crombie ◽  
Roy L. Silverstein ◽  
Clarinda MacLow ◽  
S. Frieda A. Pearce ◽  
Ralph L. Nachman ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Mononuclear Cells ◽  
Solid Phase ◽  
Peripheral Blood Mononuclear ◽  
Envelope Glycoprotein Gp120 ◽  
Whole Saliva ◽  
Thrombospondin 1 ◽  
Glycoprotein Gp120 ◽  
Hiv 1

Human and non–human primate salivas retard the infectivity of HIV-1 in vitro and in vivo. Because thrombospondin 1 (TSP1), a high molecular weight trimeric glycoprotein, is concentrated in saliva and can inhibit the infectivity of diverse pathogens in vitro, we sought to determine the role of TSP1 in suppression of HIV infectivity. Sequence analysis revealed a TSP1 recognition motif, previously defined for the CD36 gene family of cell adhesion receptors, in conserved regions flanking the disulfide-linked cysteine residues of the V3 loop of HIV envelope glycoprotein gp120, important for HIV binding to its high affinity cellular receptor CD4. Using solid-phase in vitro binding assays, we demonstrate direct binding of radiolabeled TSP1 to immobilized recombinant gp120. Based on peptide blocking experiments, the TSP1–gp120 interaction involves CSVTCG sequences in the type 1 properdin-like repeats of TSP1, the known binding site for CD36. TSP1 and fusion proteins derived from CD36-related TSP1-binding domains were able to compete with radiolabeled soluble CD4 binding to immobilized gp120. In parallel, purified TSP1 inhibited HIV-1 infection of peripheral blood mononuclear cells and transformed T and promonocytic cell lines. Levels of TSP1 required for both viral aggregation and direct blockade of HIV-1 infection were physiologic, and affinity depletion of salivary TSP1 abrogated >70% of the inhibitory effect of whole saliva on HIV infectivity. Characterization of TSP1–gp120 binding specificity suggests a mechanism for direct blockade of HIV infectivity that might be exploited to retard HIV transmission that occurs via mucosal routes.

scholarly journals Removal of two high-mannose N-linked glycans on gp120 renders human immunodeficiency virus 1 largely resistant to the carbohydrate-binding agent griffithsin

2011 ◽  
Vol 92 (10) ◽  
pp. 2367-2373 ◽  
Author(s):  
Xin Huang ◽  
Wei Jin ◽  
George E. Griffin ◽  
Robin J. Shattock ◽  
Qinxue Hu
Keyword(s):  
Human Immunodeficiency Virus ◽  
Neutralizing Antibodies ◽  
Site Directed Mutagenesis ◽  
Carbohydrate Binding ◽  
Immunodeficiency Virus ◽  
Galanthus Nivalis ◽  
High Mannose ◽  
Topical Microbicides ◽  
Marked Resistance ◽  
Hiv 1

High-mannose N-linked glycans recognized by carbohydrate-binding agents (CBAs) are potential targets for topical microbicides. To better understand the mechanisms by which CBAs inhibit human immunodeficiency virus (HIV)-1 infection at the molecular level, we systematically analysed the contribution of site-specific glycans to the anti-HIV activity of CBAs by site-directed mutagenesis. Our results demonstrate that a single deglycosylation at N295 or N448 in a range of primary and T-cell-line-adapted HIV-1 isolates resulted in marked resistance to griffithsin (GRFT) but maintained the sensitivity to cyanovirin (CV-N), Galanthus nivalis agglutinin (GNA) and a range of neutralizing antibodies. Unlike CV-N and GNA, the interaction between GRFT and gp120 appeared to be dependent on the specific trimeric ‘sugar tower’ including N295 and N448. This was further strengthened by the results of GRFT–Env binding experiments. Our study identifies GRFT-specific gp120 glycans and may provide information for the design of novel CBA antiviral strategies.

scholarly journals Activity Dependence of a Novel Lectin Family on Structure and Carbohydrate-Binding Properties

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 150 ◽  
Author(s):  
Irina Chikalovets ◽  
Alina Filshtein ◽  
Valentina Molchanova ◽  
Tatyana Mizgina ◽  
Pavel Lukyanov ◽  
...  
Keyword(s):  
Amino Acid ◽  
Sequence Analysis ◽  
Diagnostic Tools ◽  
Carbohydrate Binding ◽  
Mytilus Trossulus ◽  
Amino Acid Sequence Analysis ◽  
Binding Properties ◽  
Lectin Family ◽  
Activity Dependence ◽  
Antiproliferative Activities

A GalNAc/Gal-specific lectins named CGL and MTL were isolated and characterized from the edible mussels Crenomytilus grayanus and Mytilus trossulus. Amino acid sequence analysis of these lectins showed that they, together with another lectin MytiLec-1, formed a novel lectin family, adopting β-trefoil fold. In this mini review we discuss the structure, oligomerization, and carbohydrate-binding properties of a novel lectin family. We describe also the antibacterial, antifungal, and antiproliferative activities of these lectins and report about dependence of activities on molecular properties. Summarizing, CGL, MTL, and MytiLec-1 could be involved in the immunity in mollusks and may become a basis for the elaboration of new diagnostic tools or treatments for a variety of cancers.

scholarly journals Actinohivin, a Broadly Neutralizing Prokaryotic Lectin, Inhibits HIV-1 Infection by Specifically Targeting High-Mannose-Type Glycans on the gp120 Envelope

2010 ◽  
Vol 54 (8) ◽  
pp. 3287-3301 ◽  
Author(s):  
Bart Hoorelbeke ◽  
Dana Huskens ◽  
Geoffrey Férir ◽  
Katrien O. François ◽  
Atsushi Takahashi ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cell Cultures ◽  
Glycosylation Site ◽  
Carbohydrate Binding ◽  
Potential Candidate ◽  
Activation Markers ◽  
Neutralizing Activity ◽  
Immunodeficiency Virus ◽  
High Mannose ◽  
Hiv 1

ABSTRACT The lectin actinohivin (AH) is a monomeric carbohydrate-binding agent (CBA) with three carbohydrate-binding sites. AH strongly interacts with gp120 derived from different X4 and R5 human immunodeficiency virus (HIV) strains, simian immunodeficiency virus (SIV) gp130, and HIV type 1 (HIV-1) gp41 with affinity constants (KD ) in the lower nM range. The gp120 and gp41 binding of AH is selectively reversed by (α1,2-mannose)3 oligosaccharide but not by α1,3/α1,6-mannose- or GlcNAc-based oligosaccharides. AH binding to gp120 prevents binding of α1,2-mannose-specific monoclonal antibody 2G12, and AH covers a broader epitope on gp120 than 2G12. Prolonged exposure of HIV-1-infected CEM T-cell cultures with escalating AH concentrations selects for mutant virus strains containing N-glycosylation site deletions (predominantly affecting high-mannose-type glycans) in gp120. In contrast to 2G12, AH has a high genetic barrier, since several concomitant N-glycosylation site deletions in gp120 are required to afford significant phenotypic drug resistance. AH is endowed with broadly neutralizing activity against laboratory-adapted HIV strains and a variety of X4 and/or R5 HIV-1 clinical clade isolates and blocks viral entry within a narrow concentration window of variation (∼5-fold). In contrast, the neutralizing activity of 2G12 varied up to 1,000-fold, depending on the virus strain. Since AH efficiently prevents syncytium formation in cocultures of persistently HIV-1-infected HuT-78 cells and uninfected CD4+ T lymphocytes, inhibits dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-mediated capture of HIV-1 and subsequent virus transmission to CD4+ T lymphocytes, does not upregulate cellular activation markers, lacks mitogenic activity, and does not induce cytokines/chemokines in peripheral blood mononuclear cell cultures, it should be considered a potential candidate drug for microbicidal use.

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