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 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 Role of Neuraminidase in Influenza A(H7N9) Virus Receptor Binding

2017 ◽  
Vol 91 (11) ◽  
Author(s):  
Donald J. Benton ◽  
Stephen A. Wharton ◽  
Stephen R. Martin ◽  
John W. McCauley
Keyword(s):  
Sialic Acid ◽  
Cell Surface ◽  
Binding Site ◽  
Influenza A Virus ◽  
Receptor Binding ◽  
Influenza A ◽  
Health Concern ◽  
H7n9 Virus ◽  
Virus Receptor ◽  
Sialic Acid Receptors

ABSTRACT Influenza A(H7N9) viruses have caused a large number of zoonotic infections since their emergence in 2013. They remain a public health concern due to the repeated high levels of infection with these viruses and their perceived pandemic potential. A major factor that determines influenza A virus fitness and therefore transmissibility is the interaction of the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) with the cell surface receptor sialic acid. Typically, the HA is responsible for binding to the sialic acid to allow virus internalization and the NA is a sialidase responsible for cleaving sialic acid to aid virus spread and release. N9 NA has previously been shown to have receptor binding properties mediated by a sialic acid binding site, termed the hemadsorption (Hb) site, which is discrete from the enzymatically active sialidase site. This study investigated the N9 NA from a zoonotic H7N9 virus strain in order to determine its possible role in virus receptor binding. We demonstrate that this N9 NA has an active Hb site which binds to sialic acid, which enhances overall virus binding to sialic acid receptor analogues. We also show that the N9 NA can also contribute to receptor binding due to unusual kinetic characteristics of the sialidase site which specifically enhance binding to human-like α2,6-linked sialic acid receptors. IMPORTANCE The interaction of influenza A virus glycoproteins with cell surface receptors is a major determinant of infectivity and therefore transmissibility. Understanding these interactions is important for understanding which factors are necessary to determine pandemic potential. Influenza A viruses generally mediate binding to cell surface sialic acid receptors via the hemagglutinin (HA) glycoprotein, with the neuraminidase (NA) glycoprotein being responsible for cleaving the receptor to allow virus release. Previous studies showed that the NA proteins of the N9 subtype can bind sialic acid via a separate binding site distinct from the sialidase active site. This study demonstrates for purified protein and virus that the NA of the zoonotic H7N9 viruses has a binding capacity via both the secondary binding site and unusual kinetic properties of the sialidase site which promote receptor binding via this site and which enhance binding to human-like receptors. This could have implications for understanding human-to-human transmission of these viruses.

scholarly journals Second Sialic Acid Binding Site in Newcastle Disease Virus Hemagglutinin-Neuraminidase: Implications for Fusion

2004 ◽  
Vol 78 (7) ◽  
pp. 3733-3741 ◽  
Author(s):  
Viatcheslav Zaitsev ◽  
Mark von Itzstein ◽  
Darrin Groves ◽  
Milton Kiefel ◽  
Toru Takimoto ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Newcastle Disease Virus ◽  
Binding Site ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Surface Glycoprotein ◽  
Crystal Forms ◽  
Sialic Acid Receptors ◽  
Sialic Acid Binding ◽  
Infected Cells

ABSTRACT Paramyxoviruses are the leading cause of respiratory disease in children. Several paramyxoviruses possess a surface glycoprotein, the hemagglutinin-neuraminidase (HN), that is involved in attachment to sialic acid receptors, promotion of fusion, and removal of sialic acid from infected cells and progeny virions. Previously we showed that Newcastle disease virus (NDV) HN contained a pliable sialic acid recognition site that could take two states, a binding state and a catalytic state. Here we present evidence for a second sialic acid binding site at the dimer interface of HN and present a model for its involvement in cell fusion. Three different crystal forms of NDV HN now reveal identical tetrameric arrangements of HN monomers, perhaps indicative of the tetramer association found on the viral surface.

Avian influenza and sialic acid receptors: more than meets the eye?

2005 ◽  
Vol 5 (3) ◽  
pp. 184-188 ◽  
Author(s):  
S OLOFSSON ◽  
U KUMLIN ◽  
K DIMOCK ◽  
N ARNBERG
Keyword(s):  
Sialic Acid ◽  
Avian Influenza ◽  
Sialic Acid Receptors

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.

Recognition in Novel Molecularly Imprinted Polymer Sialic Acid Receptors in Aqueous Media

1996 ◽  
Vol 29 (7) ◽  
pp. 1099-1107 ◽  
Author(s):  
Akimitsu Kugimiya∗ ◽  
Toshifumi Takeuchi ◽  
Jun Matsuib ◽  
Kazunori Ikebukuro ◽  
Kazuyoshi Yano ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Molecularly Imprinted Polymer ◽  
Aqueous Media ◽  
Imprinted Polymer ◽  
Molecularly Imprinted ◽  
Sialic Acid Receptors

scholarly journals Antiviral adhesion molecular mechanisms for influenza: W. G. Laver's lifetime obsession

2015 ◽  
Vol 370 (1661) ◽  
pp. 20140034 ◽  
Author(s):  
Elspeth F. Garman
Keyword(s):  
Sialic Acid ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Surface Protein ◽  
X Ray Crystallography ◽  
Sialic Acid Receptors ◽  
Sialic Acid Binding ◽  
Viral Surface Protein ◽  
Viral Surface

Infection by the influenza virus depends firstly on cell adhesion via the sialic-acid-binding viral surface protein, haemagglutinin, and secondly on the successful escape of progeny viruses from the host cell to enable the virus to spread to other cells. To achieve the latter, influenza uses another glycoprotein, the enzyme neuraminidase (NA), to cleave the sialic acid receptors from the surface of the original host cell. This paper traces the development of anti-influenza drugs, from the initial suggestion by MacFarlane Burnet in 1948 that an effective ‘competitive poison’ of the virus' NA might be useful in controlling infection by the virus, through to the determination of the structure of NA by X-ray crystallography and the realization of Burnet's idea with the design of NA inhibitors. A focus is the contribution of the late William Graeme Laver, FRS, to this research.

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
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