scholarly journals Identification of Potential Binding Sites of Sialic Acids on the RBD Domain of SARS-CoV-2 Spike Protein

2021 ◽  
Vol 9 ◽  
Author(s):  
Bingqian Li ◽  
Lin Wang ◽  
Huan Ge ◽  
Xianglei Zhang ◽  
Penxuan Ren ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Binding Sites ◽  
Sialic Acids ◽  
Host Cells ◽  
Spike Protein ◽  
Molecular Probe ◽  
Acetylneuraminic Acid ◽  
Mass Spectrum Analysis ◽  
Multiple Receptors ◽  
Potential Binding

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still an emergent pandemic for humans. The virus infection is achieved by penetrating its spike protein to host cells via binding with ACE2. Moreover, recent studies show that SARS-CoV-2 may have multiple receptors that need to be further revealed. SARS-CoV-2 shares similar sequences of the spike protein with the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which can invade host cells by binding to either DPP4 or sialic acids. Sialic acids can be linked to the terminal of glycoproteins and gangliosides are used as one of the receptors of many types of viruses. Therefore, it is very interesting to determine whether sialic acid is a potential receptor of SARS-CoV-2. To address this question, we took N-Acetylneuraminic acid (Neu5Ac), a type of predominant sialic acid found in human cells, as the molecular probe to computationally search the surface of the spike protein to locate the potential binding sites of Neu5Ac. SPR analysis and mass spectrum analysis confirmed the interaction between Neu5Ac and spike protein. This study shows that sialic acids can moderately interact with the spike protein of SARS-CoV-2 by binding between the two RBDs of the spike protein, indicating it could be a potential secondary or auxiliary receptor of SARS-CoV-2.

Sialic Acid (N-Acetylneuraminic Acid) in Human Serum

1964 ◽  
Vol 10 (11) ◽  
pp. 986-990 ◽  
Author(s):  
J A Cabezas ◽  
J Vazquez Porto
Keyword(s):  
Sialic Acid ◽  
Rheumatic Disease ◽  
Human Serum ◽  
Spectrophotometric Method ◽  
Butyl Acetate ◽  
Normal Values ◽  
Sialic Acids ◽  
Old Adults ◽  
Acetylneuraminic Acid ◽  
Severe Burns

Abstract A simple spectrophotometric method is described for the sialic acids which utilizes the reaction with resorcinol and extraction with butyl acetate-n-butanol as a solvent. Normal values for adults, utilizing N-acetylneuraminic acid as a standard, were found to be 60 ± 10.4 mg./100 ml. Values for newborn babies averaged 40.4 ± 5.7. Similar values were found for specimens from 2-month-old infants to 27-year-old adults. Higher values were noted in the case of rickets, severe burns, rheumatic disease, and tuberculosis.

scholarly journals Targeting the GRP78-Dependant SARS-CoV-2 Cell Entry by Peptides and Small Molecules

2020 ◽  
Vol 14 ◽  
pp. 117793222096550
Author(s):  
Loubna Allam ◽  
Fatima Ghrifi ◽  
Hakmi Mohammed ◽  
Naima El Hafidi ◽  
Rachid El Jaoudi ◽  
...  
Keyword(s):  
Small Molecules ◽  
Binding Sites ◽  
Epigallocatechin Gallate ◽  
Host Cells ◽  
Spike Protein ◽  
Target Cells ◽  
Binding Affinities ◽  
Rapid Spread ◽  
Inhibitor Compounds ◽  
Potential Inhibitors

The global burden of infections and the rapid spread of viral diseases show the need for new approaches in the prevention and development of effective therapies. To this end, we aimed to explore novel inhibitor compounds that can stop replication or decrease the viral load of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there is currently no approved treatment. Besides using the angiotensin-converting enzyme (ACE2) receptor as a main gate, the CoV-2 can bind to the glucose-regulating protein 78 (GRP78) receptor to get into the cells to start an infection. Here, we report potential inhibitors comprising small molecules and peptides that could interfere with the interaction of SARS-CoV-2 and its target cells by blocking the recognition of the GRP78 cellular receptor by the viral Spike protein. These inhibitors were discovered through an approach of in silico screening of available databases of bioactive peptides and polyphenolic compounds and the analysis of their docking modes. This process led to the selection of 9 compounds with optimal binding affinities to the target sites. The peptides (satpdb18674, satpdb18446, satpdb12488, satpdb14438, and satpdb28899) act on regions III and IV of the viral Spike protein and on its binding sites in GRP78. However, 4 polyphenols such as epigallocatechin gallate (EGCG), homoeriodictyol, isorhamnetin, and curcumin interact, in addition to the Spike protein and its binding sites in GRP78, with the ATPase domain of GRP78. Our work demonstrates that there are at least 2 approaches to block the spread of SARS-CoV-2 by preventing its fusion with the host cells via GRP78.

scholarly journals The structure of siglec-7 in complex with sialosides: leads for rational structure-based inhibitor design

2006 ◽  
Vol 397 (2) ◽  
pp. 271-278 ◽  
Author(s):  
Helen Attrill ◽  
Hirokazu Takazawa ◽  
Simone Witt ◽  
Soerge Kelm ◽  
Rainer Isecke ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Binding Sites ◽  
Cellular Interactions ◽  
Inhibitor Design ◽  
Binding Assays ◽  
Rational Structure ◽  
Transmembrane Receptors ◽  
Acetylneuraminic Acid ◽  
Sialic Acid Binding ◽  
Inhibition Data

Siglecs (sialic acid binding Ig-like lectins) are transmembrane receptors for sialylated glycoconjugates that modulate cellular interactions and signalling events in the haematopoietic, immune and nervous systems. Siglec-7 is a structural prototype for the recently described family of immune inhibitory CD33-related siglecs and is predominantly expressed on natural killer cells and monocytes, as well as subsets of CD8 T-cells. Siglec-specific inhibitors are desired for the detection of masked and unmasked forms of siglecs, to aid in dissection of signalling pathways and as tools to investigate siglecs as potential therapeutic targets. As a first step towards this end, we present the crystal structure of siglec-7 in complex with a sialylated ligand, the ganglioside analogue DSLc4 [α(2,3)/α(2,6) disialyl lactotetraosyl 2-(trimethylsilyl)ethyl], which allows for a detailed description of the binding site, required for structure-guided inhibitor design. Mutagenesis and binding assays were used to demonstrate a key structural role for Lys131, a residue that changes conformation upon sialic acid binding. Differences between the binding sites of siglec family members were then exploited using α-methyl Neu5Ac (N-acetylneuraminic acid) as a basic scaffold. A co-crystal of siglec-7 in complex with the sialoside inhibitor, oxamido-Neu5Ac [methyl α-9-(amino-oxalyl-amino)-9-deoxy-Neu5Ac] and inhibition data for the sialosides gives clear leads for future inhibitor design.

scholarly journals Sialic acid acquisition in bacteria–one substrate, many transporters

2016 ◽  
Vol 44 (3) ◽  
pp. 760-765 ◽  
Author(s):  
Gavin H. Thomas
Keyword(s):  
Sialic Acid ◽  
Immune Evasion ◽  
Sialic Acids ◽  
Major Facilitator Superfamily ◽  
Acid Uptake ◽  
Gram Negative Bacteria ◽  
Acetylneuraminic Acid ◽  
Wide Range ◽  
Major Facilitator

The sialic acids are a family of 9-carbon sugar acids found predominantly on the cell-surface glycans of humans and other animals within the Deuterostomes and are also used in the biology of a wide range of bacteria that often live in association with these animals. For many bacteria sialic acids are simply a convenient source of food, whereas for some pathogens they are also used in immune evasion strategies. Many bacteria that use sialic acids derive them from the environment and so are dependent on sialic acid uptake. In this mini-review I will describe the discovery and characterization of bacterial sialic acids transporters, revealing that they have evolved multiple times across multiple diverse families of transporters, including the ATP-binding cassette (ABC), tripartite ATP-independent periplasmic (TRAP), major facilitator superfamily (MFS) and sodium solute symporter (SSS) transporter families. In addition there is evidence for protein-mediated transport of sialic acids across the outer membrane of Gram negative bacteria, which can be coupled to periplasmic processing of different sialic acids to the most common form, β-D-N-acetylneuraminic acid (Neu5Ac) that is most frequently taken up into the cell.

scholarly journals Elucidation of the topological parameters of N-acetylneuraminic acid and some analogues involved in their interaction with the N-acetylneuraminate lyase from Clostridium perfringens

1992 ◽  
Vol 282 (2) ◽  
pp. 511-516 ◽  
Author(s):  
E Zbiral ◽  
R G Kleineidam ◽  
E Schreiner ◽  
M Hartmann ◽  
R Christian ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Oxygen Atom ◽  
Clostridium Perfringens ◽  
Pyruvic Acid ◽  
Sialic Acids ◽  
Side Chain ◽  
Equatorial Zone ◽  
Enzyme Action ◽  
Acetylneuraminic Acid ◽  
Topological Parameters

A series of neuraminic acid derivatives modified in the side chain or at C-3, C-4 or C-5 were tested as substrates of inhibitors of N-acetylneuraminate lyase (EC 4.1.3.3) from Clostridium perfringens. The results, together with Km and Ki values reported previously, indicate that the region most important for the binding of sialic acids is an equatorial zone reaching from C-8 via the ring oxygen atom to C-4 of the sugar molecule, whereas the substituents at C-9 and C-5 may be varied to a higher extent without significantly disturbing enzyme action. It is shown that stereo-electronic factors are responsible for the immediate heterolytic fragmentation of the cyclic sialic acid into pyruvic acid and 2-acetamidomannose or a related C-6 sugar.

scholarly journals Attachment of Mouse Hepatitis Virus to O-Acetylated Sialic Acid Is Mediated by Hemagglutinin-Esterase and Not by the Spike Protein

2010 ◽  
Vol 84 (17) ◽  
pp. 8970-8974 ◽  
Author(s):  
Martijn A. Langereis ◽  
Arno L. W. van Vliet ◽  
Willemijn Boot ◽  
Raoul J. de Groot
Keyword(s):  
Sialic Acid ◽  
Hepatitis Virus ◽  
Mouse Hepatitis Virus ◽  
Protein S ◽  
Sialic Acids ◽  
The Other ◽  
Spike Protein ◽  
Apparent Contrast ◽  
Group A ◽  
New Hosts

ABSTRACT The members of Betacoronavirus phylocluster A possess two types of surface projections, one comprised of the spike protein (S) and the other of hemagglutinin-esterase (HE). Purportedly, these viruses bind to O-acetylated sialic acids (O-Ac-Sias) primarily through S, with HE serving merely as receptor-destroying enzyme. Here, we show that, in apparent contrast to human and ungulate host range variants of Betacoronavirus-1, murine coronaviruses actually bind to O-Ac-Sias via HE exclusively. Apparently, expansion of group A betacoronaviruses into new hosts and niches was accompanied by changes in HE ligand and substrate preference and in the roles of HE and S in Sia receptor usage.

scholarly journals The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2

2020 ◽  
Author(s):  
Erik Procko
Keyword(s):  
Receptor Binding ◽  
Binding Sites ◽  
Protein S ◽  
Public Health Emergency ◽  
Host Cells ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Sars Coronavirus ◽  
Molecular Events ◽  
Proteins And Peptides

SUMMARYThe rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency. The viral spike protein S binds ACE2 on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S. Mutations are found across the interface, in the N90-glycosylation motif, and at buried sites where they are predicted to enhance local folding and presentation of the interaction epitope. When single substitutions are combined, large increases in binding can be achieved. The mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedented challenge.

A method for the simultaneous estimation of free and ketosidically bound sialic acids

1977 ◽  
Vol 55 (7) ◽  
pp. 778-782 ◽  
Author(s):  
C. F. A. Culling ◽  
P. E. Reid ◽  
C. W. Ramey ◽  
W. L. Dunn ◽  
M. G. Clay
Keyword(s):  
Sialic Acid ◽  
Room Temperature ◽  
Thiobarbituric Acid ◽  
Sialic Acids ◽  
Simultaneous Estimation ◽  
Sodium Metaperiodate ◽  
Acetylneuraminic Acid ◽  
Acid Reagent ◽  
Bovine Submaxillary Mucin ◽  
Free Sialic Acid

Various methods for the estimation of free and ketosidically bound sialic acid were investigated for accuracy and specificity. It was found that oxidation with 0.025 M sodium metaperiodate in pH 7.0 phosphate buffer at room temperature for 20 min provided a simple, rapid, sensitive method whereby both the free and the ketosidically bound acid present in a mixture could be quantitatively analyzed. On completion of the oxidation step, the bound sialic acid is estimated with resorcinol reagent and the free sialic acid with thiobarbituric acid reagent. Oxidation under these conditions permitted a facile analysis of mixtures of bovine submaxillary mucin and free N-acetylneuraminic acid, whereas the Warren thiobarbituric acid procedure gave an erroneous value for free sialic acid.

The Inhibitory Effect of Sialic Acid on Fibrinolysis

1967 ◽  
Vol 17 (01/02) ◽  
pp. 023-030 ◽  
Author(s):  
H Rubin ◽  
N. D Ritz
Keyword(s):  
Sialic Acid ◽  
Inhibitory Effect ◽  
Sialic Acids ◽  
Normal Serum ◽  
The Body ◽  
Inhibitory Effects ◽  
Acetylneuraminic Acid ◽  
Heated Plates ◽  
Hydrolysis Of ◽  
Fibrinolytic Action

SummaryThe inhibitory effect of N-acetylneuraminic acid and glycolyl neuramaminic acids on the hydrolysis of 51Cr tagged casein by plasmin and α-chymotrypsin has been demonstrated. N,O-diacetylneuraminic acid was ineffective. The inhibitory effect was increased by an increase in ionic strength of the reaction mixture. The two active sialic acids also inhibited the fibrinolytic action of human plasmin on heated and unheated bovine fibrin plates. The greater inhibition noted on heated plates may indicate a primary effect on plasmin rather than on activators of plasmin. The inhibitory effects of N-acetyl neuraminic acid appeared to be potentiated by normal serum inhibitors. Sialic acid did not influence the conversion of fibrin monomer to polymer.N-acetylneuraminic acid may play an important role in preserving the integrity of fibrin deposits in the body.

Sign in / Sign up

Export Citation Format

Share Document