scholarly journals Combinatorial Design of a Sialic Acid-Imprinted Binding Site

ACS Omega ◽  
2021 ◽  
Author(s):  
Liliia Mavliutova ◽  
Elena Verduci ◽  
Sudhirkumar A. Shinde ◽  
Börje Sellergren
Keyword(s):  
Sialic Acid ◽  
Binding Site ◽  
Combinatorial Design

scholarly journals Combinatorial design of a sialic acid imprinted binding site exploring a dual ion receptor approach

RSC Advances ◽  
2021 ◽  
Vol 11 (54) ◽  
pp. 34329-34337
Author(s):  
Liliia Mavliutova ◽  
Elena Verduci ◽  
Börje Sellergren
Keyword(s):  
Sialic Acid ◽  
Crown Ether ◽  
Binding Site ◽  
Combinatorial Design ◽  
Sialic Acid Receptors ◽  
Ion Imprinting

Dual-ion imprinting of sialic acid via cooperatively acting ureido- and crown ether functionalities leads to charge neutral sialic acid receptors with strong sialoglycopeptide affinity.

scholarly journals Potent sialic acid inhibitors that target influenza A virus hemagglutinin

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Jen Chang ◽  
Cheng-Yun Yeh ◽  
Ju-Chien Cheng ◽  
Yu-Qi Huang ◽  
Kai-Cheng Hsu ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Antiviral Activity ◽  
Binding Site ◽  
Influenza A Virus ◽  
Receptor Binding ◽  
Influenza A ◽  
The United States ◽  
Ligand Complex ◽  
Receptor Binding Site ◽  
Computational Strategy

AbstractEradicating influenza A virus (IAV) is difficult, due to its genetic drift and reassortment ability. As the infectious cycle is initiated by the influenza glycoprotein, hemagglutinin (HA), which mediates the binding of virions to terminal sialic acids moieties, HA is a tempting target of anti-influenza inhibitors. However, the complexity of the HA structure has prevented delineation of the structural characterization of the HA protein–ligand complex. Our computational strategy efficiently analyzed > 200,000 records of compounds held in the United States National Cancer Institute (NCI) database and identified potential HA inhibitors, by modeling the sialic acid (SA) receptor binding site (RBS) for the HA structure. Our modeling revealed that compound NSC85561 showed significant antiviral activity against the IAV H1N1 strain with EC50 values ranging from 2.31 to 2.53 µM and negligible cytotoxicity (CC50 > 700 µM). Using the NSC85561 compound as the template to generate 12 derivatives, robust bioassay results revealed the strongest antiviral efficacies with NSC47715 and NSC7223. Virtual screening clearly identified three SA receptor binding site inhibitors that were successfully validated in experimental data. Thus, our computational strategy has identified SA receptor binding site inhibitors against HA that show IAV-associated antiviral activity.

scholarly journals Neutrophils do not bind to or phagocytize human immune complexes formed with influenza virus

Blood ◽  
1993 ◽  
Vol 82 (5) ◽  
pp. 1639-1646 ◽  
Author(s):  
DR Ratcliffe ◽  
J Michl ◽  
EB Cramer
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Epithelial Cells ◽  
Binding Site ◽  
Immune Complexes ◽  
Human Neutrophils ◽  
Sialic Acid Binding ◽  
Infected Cells ◽  
Neutrophil Adherence ◽  
Human Immune

Abstract Neutrophils appear to form the first line of defense against influenza virus, yet it is unclear how these leukocytes recognize influenza- infected cells. While demonstrating that neutrophils adhere specifically to the sialic acid-binding site on the hemagglutinin molecule (HA) on the surface of influenza-infected (WSN[H1N1]) epithelial cells and not to other viral or epithelial cell antigens, it was observed that human neutrophils do not recognize immune complexes formed with influenza virus. Intact antibodies (mouse monoclonal antibodies [MoAbs] IgG1 and IgG2b, human immune heat-inactivated serum [predominantly IgG1], and IgG purified from human immune serum) that block the sialic acid-binding site on HA significantly reduced (> 80%) neutrophil adherence to influenza-infected epithelial cells. Binding and phagocytosis of free influenza virions and neutrophil agglutination by influenza virus were completely prevented by these antibodies. Intact and F(ab')2 fragments of mouse MoAbs to other viral epitopes caused increased neutrophil adherence to infected cells. This binding was eliminated by F(ab'2) fragments of MoAbs against the sialic acid- binding site on HA, but not by saturating amounts of MoAbs, which block the neutrophil Fc receptors. Thus, it appears that human neutrophils show little ability to bind via their Fc receptors to the immune complexes formed with antibody and either influenza-infected epithelial cells or the free virion. These findings are in contrast to the general dogma, and are the first example of antibody opsonization reducing, rather than enhancing, neutrophil binding and phagocytosis of a pathogen.

A Secondary Sialic Acid Binding Site on Influenza Virus Neuraminidase: Fact or Fiction?

2012 ◽  
Vol 51 (9) ◽  
pp. 2221-2224 ◽  
Author(s):  
Jimmy C. C. Lai ◽  
Jean-Michel Garcia ◽  
Jeffrey C. Dyason ◽  
Raphael Böhm ◽  
Paul D. Madge ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Binding Site ◽  
Sialic Acid Binding ◽  
Influenza Virus Neuraminidase

scholarly journals Characterization of the Sialic Acid-binding Site in Sialoadhesin by Site-directed Mutagenesis

1996 ◽  
Vol 271 (16) ◽  
pp. 9267-9272 ◽  
Author(s):  
Mary Vinson ◽  
P. Anton van der Merwe ◽  
Sørge Kelm ◽  
Andy May ◽  
E. Yvonne Jones ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Binding Site ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Sialic Acid Binding

scholarly journals Bacterial periplasmic sialic acid-binding proteins exhibit a conserved binding site

2014 ◽  
Vol 70 (7) ◽  
pp. 1801-1811 ◽  
Author(s):  
Thanuja Gangi Setty ◽  
Christine Cho ◽  
Sowmya Govindappa ◽  
Michael A. Apicella ◽  
S. Ramaswamy
Keyword(s):  
Sialic Acid ◽  
Binding Site ◽  
Pathogenic Bacteria ◽  
Pasteurella Multocida ◽  
Binding Proteins ◽  
Molecular Mimicry ◽  
Binding Pocket ◽  
Sialic Acids ◽  
Host Immune System ◽  
Binding Affinities

Sialic acids are a family of related nine-carbon sugar acids that play important roles in both eukaryotes and prokaryotes. These sialic acids are incorporated/decorated onto lipooligosaccharides as terminal sugars in multiple bacteria to evade the host immune system. Many pathogenic bacteria scavenge sialic acids from their host and use them for molecular mimicry. The first step of this process is the transport of sialic acid to the cytoplasm, which often takes place using a tripartite ATP-independent transport system consisting of a periplasmic binding protein and a membrane transporter. In this paper, the structural characterization of periplasmic binding proteins from the pathogenic bacteriaFusobacterium nucleatum,Pasteurella multocidaandVibrio choleraeand their thermodynamic characterization are reported. The binding affinities of several mutations in the Neu5Ac binding site of theHaemophilus influenzaeprotein are also reported. The structure and the thermodynamics of the binding of sugars suggest that all of these proteins have a very well conserved binding pocket and similar binding affinities. A significant conformational change occurs when these proteins bind the sugar. While the C1 carboxylate has been identified as the primary binding site, a second conserved hydrogen-bonding network is involved in the initiation and stabilization of the conformational states.

scholarly journals Structural evidence for a second sialic acid binding site in avian influenza virus neuraminidases

1997 ◽  
Vol 94 (22) ◽  
pp. 11808-11812 ◽  
Author(s):  
J. N. Varghese ◽  
P. M. Colman ◽  
A. van Donkelaar ◽  
T. J. Blick ◽  
A. Sahasrabudhe ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Sialic Acid ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Binding Site ◽  
Sialic Acid Binding

scholarly journals Localization of the Putative Sialic Acid-binding Site on the Immunoglobulin Superfamily Cell-surface Molecule CD22

1996 ◽  
Vol 271 (16) ◽  
pp. 9273-9280 ◽  
Author(s):  
P. Anton van der Merwe ◽  
Paul R. Crocker ◽  
Mary Vinson ◽  
A. Neil Barclay ◽  
Roland Schauer ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Cell Surface ◽  
Binding Site ◽  
Immunoglobulin Superfamily ◽  
Surface Molecule ◽  
Cell Surface Molecule ◽  
Sialic Acid Binding

scholarly journals The Amino-terminal Immunoglobulin-like Domain of Sialoadhesin Contains the Sialic Acid Binding Site

1995 ◽  
Vol 270 (44) ◽  
pp. 26184-26191 ◽  
Author(s):  
Deepa Nath ◽  
P. Anton van der Merwe ◽  
Sørge Kelm ◽  
Paul Bradfield ◽  
Paul R. Crocker
Keyword(s):  
Sialic Acid ◽  
Binding Site ◽  
Amino Terminal ◽  
Sialic Acid Binding
Sign in / Sign up

Export Citation Format

Share Document