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1.
Bioconjug Chem ; 33(8): 1574-1583, 2022 Aug 17.
Article in English | MEDLINE | ID: covidwho-1977960

ABSTRACT

The pentasaccharide Fondaparinux, a synthetic selective factor Xa inhibitor, is one of the safest anticoagulants in the heparin family that is recommended as an alternative drug for patients with hypersensitivity to other drugs such as heparin-induced thrombocytopenia (HIT). However, some observations of Fondaparinux-induced thrombocytopenia (FIT) have been reported while others claimed that FIT does not occur in patients with fondaparinux therapy, indicating that the mechanism of FIT remains controversial. Here, we utilized different methodologies including dynamic light scattering, immunosorbent and platelet aggregation assays, confocal laser scanning microscopy, and flow cytometry to gain insights into FIT. We found that at a certain concentration, Fondaparinux formed sufficient large and stable complexes with PF4 that facilitated binding of the HIT-like monoclonal KKO antibody and enhanced platelet aggregation and activation. We proposed a model to describe the role of Fondaparinux concentration in the formation of complexes with platelet factor 4 and how it promotes the binding of KKO. Our results clarify controversial observations of FIT in patients as each contains a dissimilar PF4:Fondaparinux concentration ratio.


Subject(s)
Thrombocytopenia , Antibodies, Monoclonal/therapeutic use , Anticoagulants/adverse effects , Fondaparinux/adverse effects , Heparin/adverse effects , Humans , Platelet Factor 4/metabolism , Platelet Factor 4/therapeutic use , Polysaccharides , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy
2.
J Virol ; 96(15): e0095822, 2022 08 10.
Article in English | MEDLINE | ID: covidwho-1949998

ABSTRACT

The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to other members of the Coronaviridae family. We also show that these spike NTD (S-NTD) proteins adhere to Calu3 cells, a human lung cell line, although the biological relevance of this is unclear. In contrast to what has been shown for Middle East respiratory syndrome coronavirus (MERS-CoV), which attaches sialic acids during cell entry, sialic acids present on Calu3 cells inhibited sarbecovirus infection. Therefore, while sarbecoviruses can interact with cell surface glycans similarly to other coronaviruses, their reliance on glycans for entry is different from that of other respiratory coronaviruses, suggesting sarbecoviruses and MERS-CoV have adapted to different cell types, tissues, or hosts during their divergent evolution. Our findings provide important clues for further exploring the biological functions of sarbecovirus glycan binding and adds to our growing understanding of the complex forces that shape coronavirus spike evolution. IMPORTANCE Spike N-terminal domains (S-NTD) of sarbecoviruses are highly diverse; however, their function remains largely understudied compared with the receptor-binding domains (RBD). Here, we show that sarbecovirus S-NTD can be phylogenetically clustered into five clades and exhibit various levels of glycan binding in vitro. We also show that, unlike some coronaviruses, including MERS-CoV, sialic acids present on the surface of Calu3, a human lung cell culture, inhibit SARS-CoV-2 and other sarbecoviruses. These results suggest that while glycan binding might be an ancestral trait conserved across different coronavirus families, the functional outcome during infection can vary, reflecting divergent viral evolution. Our results expand our knowledge on the biological functions of the S-NTD across diverse sarbecoviruses and provide insight on the evolutionary history of coronavirus spike.


Subject(s)
COVID-19 , Middle East Respiratory Syndrome Coronavirus , Humans , Middle East Respiratory Syndrome Coronavirus/metabolism , Polysaccharides , Receptors, Virus/metabolism , SARS-CoV-2 , Sialic Acids/metabolism , Spike Glycoprotein, Coronavirus/metabolism
3.
J Nanobiotechnology ; 20(1): 320, 2022 Jul 14.
Article in English | MEDLINE | ID: covidwho-1933142

ABSTRACT

BACKGROUND: Nanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines. RESULTS: In this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~ 300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~ 350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites. CONCLUSIONS: PRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.


Subject(s)
COVID-19 , Nanoparticles , Adjuvants, Immunologic/chemistry , COVID-19/prevention & control , Humans , Immunity , Nanoparticles/chemistry , Polysaccharides , SARS-CoV-2
4.
Immunol Rev ; 309(1): 64-74, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1922935

ABSTRACT

In this review, we discuss how IgG antibodies can modulate inflammatory signaling during viral infections with a focus on CD16a-mediated functions. We describe the structural heterogeneity of IgG antibody ligands, including subclass and glycosylation that impact binding by and downstream activity of CD16a, as well as the heterogeneity of CD16a itself, including allele and expression density. While inflammation is a mechanism required for immune homeostasis and resolution of acute infections, we focus here on two infectious diseases that are driven by pathogenic inflammatory responses during infection. Specifically, we review and discuss the evolving body of literature showing that afucosylated IgG immune complex signaling through CD16a contributes to the overwhelming inflammatory response that is central to the pathogenesis of severe forms of dengue disease and coronavirus disease 2019 (COVID-19).


Subject(s)
COVID-19 , Communicable Diseases , Humans , Immunoglobulin G/chemistry , Immunoglobulin G/metabolism , Polysaccharides/chemistry , Polysaccharides/metabolism , Receptors, IgG
5.
EBioMedicine ; 81: 104101, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1906945

ABSTRACT

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory illness named coronavirus disease 2019 (COVID-19), which is one of the main global health problems since 2019. Glycans attached to the Fc portion of immunoglobulin G (IgG) are important modulators of IgG effector functions. Fc region binds to different receptors on the surface of various immune cells, dictating the type of immune response. Here, we performed a large longitudinal study to determine whether the severity and duration of COVID-19 are associated with altered IgG glycosylation. METHODS: Using ultra-high-performance liquid chromatography analysis of released glycans, we analysed the composition of the total IgG N-glycome longitudinally during COVID-19 from four independent cohorts. We analysed 77 severe COVID-19 cases from the HR1 cohort (74% males, median age 72, age IQR 25-80); 31 severe cases in the HR2 cohort (77% males, median age 64, age IQR 41-86), 18 mild COVID-19 cases from the UK cohort (17% males, median age 50, age IQR 26-71) and 28 mild cases from the BiH cohort (71% males, median age 60, age IQR 12-78). FINDINGS: Multiple statistically significant changes in IgG glycome composition were observed during severe COVID-19. The most statistically significant changes included increased agalactosylation of IgG (meta-analysis 95% CI [0.03, 0.07], adjusted meta-analysis P= <0.0001), which regulates proinflammatory actions of IgG via complement system activation and indirectly as a lack of sialylation and decreased presence of bisecting N-acetylglucosamine on IgG (meta-analysis 95% CI [-0.11, -0.08], adjusted meta-analysis P= <0.0001), which indirectly affects antibody-dependent cell-mediated cytotoxicity. On the contrary, no statistically significant changes in IgG glycome composition were observed in patients with mild COVID-19. INTERPRETATION: The IgG glycome in severe COVID-19 patients is statistically significantly altered in a way that it indicates decreased immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the severity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in COVID-19. FUNDING: This work has been supported in part by Croatian Science Foundation under the project IP-CORONA-2020-04-2052 and Croatian National Centre of Competence in Molecular Diagnostics (The European Structural and Investment Funds grant #KK.01.2.2.03.0006), by the UKRI/MRC (Cov-0331 - MR/V027883/1) and by the National Institutes for Health Research Nottingham Biomedical Research Centre and by Ministry Of Science, Higher Education and Youth Of Canton Sarajevo, grant number 27-02-11-4375-10/21.


Subject(s)
COVID-19 , Immunoglobulin G , Adolescent , Aged , Female , Humans , Longitudinal Studies , Male , Middle Aged , Observational Studies as Topic , Polysaccharides/metabolism , SARS-CoV-2
6.
Science ; 377(6604): eabm3125, 2022 07 22.
Article in English | MEDLINE | ID: covidwho-1901907

ABSTRACT

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis.


Subject(s)
COVID-19 , Host-Pathogen Interactions , SARS-CoV-2 , Sialic Acids , Spike Glycoprotein, Coronavirus , COVID-19/transmission , Cryoelectron Microscopy , Genetic Variation , Humans , Nuclear Magnetic Resonance, Biomolecular , Polysaccharides/chemistry , Protein Binding , Protein Domains , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Sialic Acids/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics
7.
Proc Natl Acad Sci U S A ; 119(28): e2119761119, 2022 Jul 12.
Article in English | MEDLINE | ID: covidwho-1900767

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein is the prime target for vaccines, diagnostics, and therapeutic antibodies against the virus. While anchored in the viral envelope, for effective virulence, the spike needs to maintain structural flexibility to recognize the host cell surface receptors and bind to them, a property that can heavily depend upon the dynamics of the unresolved domains, most prominently the stalk. Construction of the complete, membrane-bound spike model and the description of its dynamics are critical steps in understanding the inner working of this key element of the viral infection by SARS-CoV-2. Combining homology modeling, protein-protein docking, and molecular dynamics (MD) simulations, we have developed a full spike structure in a native membrane. Multimicrosecond MD simulations of this model, the longest known single trajectory of the full spike, reveal conformational dynamics employed by the protein to explore the surface of the host cell. In agreement with cryogenic electron microscopy (cryo-EM), three flexible hinges in the stalk allow for global conformational heterogeneity of spike in the fully glycosylated system mediated by glycan-glycan and glycan-lipid interactions. The dynamical range of the spike is considerably reduced in its nonglycosylated form, confining the area explored by the spike on the host cell surface. Furthermore, palmitoylation of the membrane domain amplifies the local curvature that may prime the fusion. We show that the identified hinge regions are highly conserved in SARS coronaviruses, highlighting their functional importance in enhancing viral infection, and thereby, provide points for discovery of alternative therapeutics against the virus.


Subject(s)
COVID-19 , Host Microbial Interactions , Protein Processing, Post-Translational , Receptors, Cell Surface , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , COVID-19/virology , Glycosylation , Humans , Polysaccharides , Protein Binding , Receptors, Cell Surface/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
8.
PLoS Pathog ; 18(6): e1010590, 2022 06.
Article in English | MEDLINE | ID: covidwho-1892333

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been transmitted across all over the world, in contrast to the limited epidemic of genetically- and virologically-related SARS-CoV. However, the molecular basis explaining the difference in the virological characteristics among SARS-CoV-2 and SARS-CoV has been poorly defined. Here we identified that host sialoglycans play a significant role in the efficient spread of SARS-CoV-2 infection, while this was not the case with SARS-CoV. SARS-CoV-2 infection was significantly inhibited by α2-6-linked sialic acid-containing compounds, but not by α2-3 analog, in VeroE6/TMPRSS2 cells. The α2-6-linked compound bound to SARS-CoV-2 spike S1 subunit to competitively inhibit SARS-CoV-2 attachment to cells. Enzymatic removal of cell surface sialic acids impaired the interaction between SARS-CoV-2 spike and angiotensin-converting enzyme 2 (ACE2), and suppressed the efficient spread of SARS-CoV-2 infection over time, in contrast to its least effect on SARS-CoV spread. Our study provides a novel molecular basis of SARS-CoV-2 infection which illustrates the distinctive characteristics from SARS-CoV.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Peptidyl-Dipeptidase A/metabolism , Polysaccharides/metabolism , Protein Binding , Spike Glycoprotein, Coronavirus/metabolism
10.
Proteomics ; 22(15-16): e2100322, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1885450

ABSTRACT

Glycosylation of viral proteins is required for the progeny formation and infectivity of virtually all viruses. It is increasingly clear that distinct glycans also play pivotal roles in the virus's ability to shield and evade the host's immune system. Recently, there has been a great advancement in structural identification and quantitation of viral glycosylation, especially spike proteins. Given the ongoing pandemic and the high demand for structure analysis of SARS-CoV-2 densely glycosylated spike protein, mass spectrometry methodologies have been employed to accurately determine glycosylation patterns. There are still many challenges in the determination of site-specific glycosylation of SARS-CoV-2 viral spike protein. This is compounded by some conflicting results regarding glycan site occupancy and glycan structural characterization. These are probably due to differences in the expression systems, form of expressed spike glycoprotein, MS methodologies, and analysis software. In this review, we recap the glycosylation of spike protein and compare among various studies. Also, we describe the most recent advancements in glycosylation analysis in greater detail and we explain some misinterpretation of previously observed data in recent publications. Our study provides a comprehensive view of the spike protein glycosylation and highlights the importance of consistent glycosylation determination.


Subject(s)
COVID-19 , SARS-CoV-2 , Glycosylation , Humans , Mass Spectrometry/methods , Polysaccharides/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
11.
Anal Chem ; 94(15): 5909-5917, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1882715

ABSTRACT

SARS-CoV-2 cellular infection is mediated by the heavily glycosylated spike protein. Recombinant versions of the spike protein and the receptor-binding domain (RBD) are necessary for seropositivity assays and can potentially serve as vaccines against viral infection. RBD plays key roles in the spike protein's structure and function, and thus, comprehensive characterization of recombinant RBD is critically important for biopharmaceutical applications. Liquid chromatography coupled to mass spectrometry has been widely used to characterize post-translational modifications in proteins, including glycosylation. Most studies of RBDs were performed at the proteolytic peptide (bottom-up proteomics) or released glycan level because of the technical challenges in resolving highly heterogeneous glycans at the intact protein level. Herein, we evaluated several online separation techniques: (1) C2 reverse-phase liquid chromatography (RPLC), (2) capillary zone electrophoresis (CZE), and (3) acrylamide-based monolithic hydrophilic interaction chromatography (HILIC) to separate intact recombinant RBDs with varying combinations of glycosylations (glycoforms) for top-down mass spectrometry (MS). Within the conditions we explored, the HILIC method was superior to RPLC and CZE at separating RBD glycoforms, which differ significantly in neutral glycan groups. In addition, our top-down analysis readily captured unexpected modifications (e.g., cysteinylation and N-terminal sequence variation) and low abundance, heavily glycosylated proteoforms that may be missed by using glycopeptide data alone. The HILIC top-down MS platform holds great potential in resolving heterogeneous glycoproteins for facile comparison of biosimilars in quality control applications.


Subject(s)
Biosimilar Pharmaceuticals , COVID-19 , Chromatography, Liquid , Chromatography, Reverse-Phase/methods , Glycoproteins/chemistry , Humans , Hydrophobic and Hydrophilic Interactions , Mass Spectrometry , Polysaccharides/analysis , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry
12.
Anal Chem ; 94(15): 5776-5784, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1882709

ABSTRACT

Characterization of protein glycosylation by tandem mass spectrometry remains challenging owing to the vast diversity of oligosaccharides bound to proteins, the variation in monosaccharide linkage patterns, and the lability of the linkage between the glycan and protein. Here, we have adapted an HCD-triggered-ultraviolet photodissociation (UVPD) approach for the simultaneous localization of glycosites and full characterization of both glycan compositions and intersaccharide linkages, the latter provided by extensive cross-ring cleavages enabled by UVPD. The method is applied to study glycan compositions based on analysis of glycopeptides from proteolytic digestion of recombinant human coronaviruse spike proteins from SARS-CoV-2 and HKU1. UVPD reveals unique intersaccharide linkage information and is leveraged to localize N-linked glycoforms with confidence.


Subject(s)
COVID-19 , Viral Proteins , Glycosylation , Humans , Polysaccharides/chemistry , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Tandem Mass Spectrometry/methods , Ultraviolet Rays
13.
Biomaterials ; 286: 121585, 2022 07.
Article in English | MEDLINE | ID: covidwho-1881707

ABSTRACT

Among all the biological entities involved in the immune response, galectins, a family of glycan-binding proteins, have been described as key in immune cell homeostasis and modulation. More importantly, only some galectin family members are crucial in the resolution of inflammation, while others perpetuate the immune response in a pathological context. As they are expressed in most major diseases, their potential as targets for new therapies seems promising. Most of the galectin family members' ubiquitous expression points to the need for targeted treatments to ensure effectiveness. Engineered biomaterials are emerging as a promising method to improve galectin-targeted strategies' therapeutic performance. In this review, we provide an overview of the role of galectins in health and disease and their potential as therapeutic targets, as well as the state-of-the-art and future directions of galectin-targeted biomaterials.


Subject(s)
Biocompatible Materials , Galectins , Galectins/metabolism , Galectins/therapeutic use , Humans , Inflammation , Polysaccharides/metabolism
14.
Adv Protein Chem Struct Biol ; 131: 277-309, 2022.
Article in English | MEDLINE | ID: covidwho-1881585

ABSTRACT

Molecular Dynamics (MD) is a method used to calculate the movement of atoms and molecules broadly applied to several aspects of science. It involves computational simulation, which makes it, at first glance, not easily accessible. The rise of several automated tools to perform molecular simulations has allowed researchers to navigate through the various steps of MD. This enables to elucidate structural properties of proteins that could not be analyzed otherwise, such as the impact of glycosylation. Glycosylation dictates the physicochemical and biological properties of a protein modulating its solubility, stability, resistance to proteolysis, interaction partners, enzymatic activity, binding and recognition. Given the high conformational and compositional diversity of the glycan chains, assessing their influence on the protein structure is challenging using conventional analytical techniques. In this manuscript, we present a step-by-step workflow to build and perform MD analysis of glycoproteins focusing on the SPIKE glycoprotein of SARS-CoV-2 to appraise the impact of glycans in structure stabilization and antibody occlusion.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Glycoproteins , Humans , Molecular Dynamics Simulation , Polysaccharides/chemistry , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/metabolism
15.
Nutrients ; 14(11)2022 May 27.
Article in English | MEDLINE | ID: covidwho-1869720

ABSTRACT

Fucoidan, a sulfated polysaccharide extracted from brown seaweed, has been proposed to effectively treat and prevent various viral infections. However, the mechanisms behind its antiviral activity are not completely understood. We investigate here the global transcriptional changes in bone marrow-derived dendritic cells (BMDCs) using RNA-Seq technology. Through both analysis of differentially expressed genes (DEG) and gene set enrichment analysis (GSEA), we found that fucoidan-treated BMDCs were enriched in virus-specific response pathways, including that of SARS-CoV-2, as well as pathways associated with nucleic acid-sensing receptors (RLR, TLR, NLR, STING), and type I interferon (IFN) production. We show that these transcriptome changes are driven by well-known regulators of the inflammatory response against viruses, including IRF, NF-κB, and STAT family transcription factors. Furthermore, 435 of the 950 upregulated DEGs are classified as type I IFN-stimulated genes (ISGs). Flow cytometric analysis additionally showed that fucoidan increased MHCII, CD80, and CD40 surface markers in BMDCs, indicative of greater antigen presentation and co-stimulation functionality. Our current study suggests that fucoidan transcriptionally activates PRR signaling, type I IFN production and signaling, ISGs production, and DC maturation, highlighting a potential mechanism of fucoidan-induced antiviral activity.


Subject(s)
COVID-19 , Dendritic Cells , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Humans , Polysaccharides/metabolism , Polysaccharides/pharmacology , SARS-CoV-2
16.
Nat Commun ; 12(1): 6073, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1860369

ABSTRACT

Large-scale profiling of intact glycopeptides is critical but challenging in glycoproteomics. Data independent acquisition (DIA) is an emerging technology with deep proteome coverage and accurate quantitative capability in proteomics studies, but is still in the early stage of development in the field of glycoproteomics. We propose GproDIA, a framework for the proteome-wide characterization of intact glycopeptides from DIA data with comprehensive statistical control by a 2-dimentional false discovery rate approach and a glycoform inference algorithm, enabling accurate identification of intact glycopeptides using wide isolation windows. We further utilize a semi-empirical spectrum prediction strategy to expand the coverage of spectral libraries of glycopeptides. We benchmark our method for N-glycopeptide profiling on DIA data of yeast and human serum samples, demonstrating that DIA with GproDIA outperforms the data-dependent acquisition-based methods for glycoproteomics in terms of capacity and data completeness of identification, as well as accuracy and precision of quantification. We expect that this work can provide a powerful tool for glycoproteomic studies.


Subject(s)
Glycopeptides/analysis , Proteome/analysis , Proteomics/methods , Algorithms , Blood Proteins/chemistry , Glycoproteins/chemistry , Humans , Mass Spectrometry , Polysaccharides/chemistry , Schizosaccharomyces pombe Proteins/chemistry , Workflow
18.
Carbohydr Res ; 518: 108574, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1821162

ABSTRACT

Can envelope glycans be targeted to stop viral pandemics? Here we address this question by using molecular dynamics simulations to study the binding between 10 synthetic carbohydrate receptors (SCRs) and the 33 N-glycans most commonly found on the surfaces of enveloped viruses, including Zika virus and SARS-CoV-2. Based on association quotients derived from these simulations, we classified the SCRs as weak binders, promiscuous binders, or selective binders. The SCRs almost exclusively associate at the Man3GlcNAc2 core, which is common to all N-glycans, but the binding affinity between the SCR⋅glycan pair depends on the noncovalent interactions between the heterocycle rings and the glycan antennae. Systematic variations in the glycan and SCR structures reveal relationships that could guide the design of SCRs to attain affinity and selectivity towards a chosen envelope glycan target. With these results, envelope glycans, which are currently considered "undruggable", could become viable targets for new therapeutic strategies.


Subject(s)
COVID-19 , Receptors, Artificial , Zika Virus Infection , Zika Virus , Carbohydrates/chemistry , Humans , Molecular Dynamics Simulation , Polysaccharides/chemistry , Receptors, Artificial/chemistry , SARS-CoV-2 , Zika Virus/metabolism
19.
Carbohydr Polym ; 291: 119551, 2022 Sep 01.
Article in English | MEDLINE | ID: covidwho-1814196

ABSTRACT

As a significant public health hazard with several drug side effects during medical treatment, searching for novel therapeutic natural medicines is promising. Sulfated polysaccharides from algae, such as fucoidan, have been discovered to have a variety of medical applications, including antibacterial and immunomodulatory properties. The review emphasized on the utilization of fucoidan as an antiviral agent against viral infections by inhibiting their attachment and replication. Moreover, it can also trigger immune response against viral infection in humans. This review suggested to be use the fucoidan for the potential protective remedy against COVID-19 and addressing the antiviral activities of sulfated polysaccharide, fucoidan derived from marine algae that could be used as an anti-COVID19 drug in near future.


Subject(s)
Antiviral Agents , COVID-19 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Humans , Polysaccharides/pharmacology , Polysaccharides/therapeutic use , Sulfates
20.
Molecules ; 27(9)2022 Apr 26.
Article in English | MEDLINE | ID: covidwho-1810050

ABSTRACT

Plant polysaccharides can increase the number and variety of beneficial bacteria in the gut and produce a variety of active substances, including short-chain fatty acids (SCFAs). Gut microbes and their specific metabolites have the effects of promoting anti-inflammatory activity, enhancing the intestinal barrier, and activating and regulating immune cells, which are beneficial for improving immunity. A strong immune system reduces inflammation caused by external viruses and other pathogens. Coronavirus disease 2019 (COVID-19) is still spreading globally, and patients with COVID-19 often have intestinal disease and weakened immune systems. This article mainly evaluates how polysaccharides in plants can improve the immune system barrier by improving the intestinal microecological balance, which may have potential in the prevention and treatment of COVID-19.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , COVID-19/drug therapy , Fatty Acids, Volatile/metabolism , Humans , Immunity , Polysaccharides/metabolism , Polysaccharides/pharmacology , Polysaccharides/therapeutic use
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