The 1918 Influenza A Pandemic
Patricia G. Melloy in Viruses and Society, 2023
If one examines the structure of an influenza virus, one will see two major kinds of spike proteins coming out of the envelope: the hemagglutinin (H) and neuraminidase (N) proteins. The hemagglutinin spike proteins attach to sialic acid, a type of sugar or carbohydrate, displayed on respiratory cells. The neuraminidase proteins later clear sialic acid molecules out of the way, preventing any obstacles to catch the influenza viral particles as they bud back out of the cell, thousands of viral particles at a time (Barry 2018; Brown 2018; Lostroh 2019). There are sugars bound to proteins and lipids on cell surfaces as well as on secreted molecules. Sialic acid is a type of sugar attached to the “outermost part” of the sugar chain in certain cell types. Sialic acid has a normal role in cell interactions as well as affecting protein stability. However, viral, bacterial, and parasitic pathogens can use sialic acid as a way to gain entry into cells (Varki 2008).
Host and Pathogen-Specific Drug Targets in COVID-19
Debmalya Barh, Kenneth Lundstrom in COVID-19, 2022
Sialic acids are a family of monosaccharides attached to various glycolipids and glycoproteins on epithelial cell membranes. That is why sialic acids are considered a highly accessible cell membrane component for receptor–ligand and protein–ligand interactions. In the context of virology, sialic acids were the first characterized receptors promoting the viral entry process [20]. Viral entry through the sialic acid-dependent manner has been shown in several types of coronaviruses based on enzymatic activities of hemagglutinin esterase [21]. Concerning SARS-CoV-2, specific sialic acids [22] on the respiratory tract’s epithelium could be employed as co-receptors for the S protein so that virus clustering is facilitated. Moreover, ACE2, as the primary receptor for SARS-CoV-2 attachment, is heavily sialylated on N- and O-linked sugar chains. Consequently, the sialic acid-mediating targeted therapies may inhibit SARS-CoV-2 invasion by inhibiting virus–host cell interaction and modulation of endocytosis. However, the host sialome could also play a protective role against viral infections by providing a large layer of sialylated residues on mucosal cell surfaces and interfering with virus entry by offering an alternative binding site. This section aims to summarize the potential sialic acid-mediating targeted therapies in COVID-19 and provides insight into their molecular mechanisms (Figure 10.1).
The Development of Improved Therapeutics through a Glycan- “Designer” Approach
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Other very interesting from the perspective of medicinal chemistry glycan groups (that should be rather avoided or carefully evaluated prior to usage) are sialic acids (Sias). Sialic acids are negatively charged, 9-carbon chain backbone monosaccharides, abundant in human cells and tissues. Their role ranges from cellular processes, regeneration to regulation of immune system. The key enzyme in the synthesis of sialic acids in human body is GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine-kinase. Sialic acids are one of the most diverse glycans. The variety arises from diverse α-linkages between second carbon C-2 of the sialic acids and underlying sugars. The variety of natural modifications adds up to a secondary level of their diversity. The combinations of different glycosidic linkages with multitude of possible modifications (e.g., Neu5Ac, Neu5Gc, addition of hydroxyl groups on C-4, C7, C-8, or C9) generate huge variety among sialic acids and account to distinctive glycocode of different cell types. Sialic acids modifications were linked to particular types of malignancies; for example, there is an association of N-glycolyl-neuraminic acid (Neu5Gc) prevalence on cancer tissues, yielding an inflammatory response (Pearce and Laubli, 2016). Some of the sialic acids in conjugation with highly immunogenic proteins/peptides are explored for their cancer protective vaccine application. Research in the field of sialic acids and their interaction with Siglec receptors could open many new ideas on immune regulation and cell signaling.
Evaluation of acute kidney injury with oxidative stress biomarkers and Renal Resistive Index after cardiac surgery
Published in Acta Chirurgica Belgica, 2021
Alper Kararmaz, Mustafa Kemal Arslantas, Ugur Aksu, Halim Ulugol, Ismail Cinel, Fevzi Toraman
Sialic acid is the carbohydrate moiety of glycoproteins and a component of glycocalyx [34]. In our study, CPB results to an increment of serum sialic acid levels. This could be attributed to a loss of glycocalyx integrity leading to an imbalance of redox homeostasis as mentioned with other measured biochemical parameters. By way of explanation, the ongoing results suggest that there is an association between CPB and desialylation of protein-bound sialic acid and this relation could lead to postoperative complications as kidney related injuries. Another point of these results is that removing sialic acid from receptor which called as desialylation process can affect 3D conformation of the receptor; hence, this could also affect the function of receptors. Moreover, free sialic acid molecules could be a trigger for a variety of cellular signal processes [34].
The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease
Published in International Reviews of Immunology, 2023
Shane Prenzler, Santosh Rudrawar, Mario Waespy, Sørge Kelm, Shailendra Anoopkumar-Dukie, Thomas Haselhorst
The sialic acid binding immunoglobulin-like lectins (Siglec) are a family of transmembrane proteins characterized by an extracellular domain, the transmembrane region and cytoplasmic tail [1]. Sialic acids are a family of nine-carbon acidic monosaccharides that occur naturally at the end of sugar chains attached to the surfaces of cells and soluble proteins and are ligands for Siglec proteins (Figure 1) [2]. Siglec-1, also known as CD169 and Sialoadhesin (Sn), is the first siglec family member identified. Siglec-1 is a 210 kDa type I single membrane spanning glycoprotein containing 17 immunoglobulin-like domains [1, 3]. Expression of Siglec-1 is found primarily on dendritic cells (DCs), macrophages and interferon induced monocytes [4–6]. The structure of Siglec-1 is unique among siglecs and its function as a receptor also is different compared to other receptors in this class, as it contains the most extracellular domains out of all the siglecs [7]. Sixteen of these extracellular domains are C2-set domains and the furthermost domain is the terminal V-set domain which contains the sialic acid binding pocket (Figure 2) [7]. The V-set domain of Siglec-1 is also highly conserved across vertebrate species, similar to Siglec-2 (CD22), Siglec-4 (MAG) and Siglec-15 [8]. Amino acid differences in the human and murine form of Siglec-2 necessitated the development of transgenic CD22 mice which expressed human CD22 [9].
Carbohydrates great and small, from dietary fiber to sialic acids: How glycans influence the gut microbiome and affect human health
Published in Gut Microbes, 2021
Joanna K Coker, Oriane Moyne, Dmitry A. Rodionov, Karsten Zengler
Thus far, we have discussed the impact of broad dietary glycan classes on the gut microbiome and host health, including how lack of fiber promotes microbial degradation of host mucus glycans. Next, we focus on the impact of dietary sialic acids, a unique and essential class of monosaccharides, on the gut microbiome and human health. Sialic acids are essential to many physiological processes, play a large role in shaping both the infant and adult microbiome, and allow exploration of how minor chemical modifications in sugar structure can shape the microbiome. Although many authors have reviewed sialic acids in the past, to our knowledge a comprehensive review focusing specifically on dietary sialic acids and the gut microbiome has not been published. In the literature, “sialic acids” is often used to refer to both the group and its most common member, N-acetylneuraminic acid. In this review, we will refer to N-acetylneuraminic acid by its abbreviation Neu5Ac and reserve the term sialic acids for the group as a whole.
Related Knowledge Centers
- Ganglioside
- Synaptogenesis
- Glycoprotein
- Sugar
- Carbon
- Saliva
- N-Acetylneuraminic Acid
- Regulation of Gene Expression
- Glycoconjugate
- Neuraminic Acid