scholarly journals Structural Insight into Non-Enveloped Virus Binding to Glycosaminoglycan Receptors: A Review

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 800
Author(s):  
Marie N. Sorin ◽  
Jasmin Kuhn ◽  
Aleksandra C. Stasiak ◽  
Thilo Stehle
Keyword(s):  
Host Cell ◽  
Viral Entry ◽  
Structural Information ◽  
Sialic Acids ◽  
Virus Binding ◽  
Enveloped Virus ◽  
Charged Amino Acids ◽  
Current State ◽  
Human Viruses ◽  
Viral Receptors

Viruses are infectious agents that hijack the host cell machinery in order to replicate and generate progeny. Viral infection is initiated by attachment to host cell receptors, and typical viral receptors are cell-surface-borne molecules such as proteins or glycan structures. Sialylated glycans (glycans bearing sialic acids) and glycosaminoglycans (GAGs) represent major classes of carbohydrate receptors and have been implicated in facilitating viral entry for many viruses. As interactions between viruses and sialic acids have been extensively reviewed in the past, this review provides an overview of the current state of structural knowledge about interactions between non-enveloped human viruses and GAGs. We focus here on adeno-associated viruses, human papilloma viruses (HPVs), and polyomaviruses, as at least some structural information about the interactions of these viruses with GAGs is available. We also discuss the multivalent potential for GAG binding, highlighting the importance of charged interactions and positively charged amino acids at the binding sites, and point out challenges that remain in the field.

HAZARD: An Expert System for Risk Assessment of Environmental Chemicals

1987 ◽  
Vol 26 (01) ◽  
pp. 13-23 ◽  
Author(s):  
H. W. Gottinger
Keyword(s):  
Expert System ◽  
Structural Information ◽  
Chemical Carcinogenesis ◽  
Structural Features ◽  
Environmental Chemicals ◽  
Chemical Carcinogens ◽  
Carcinogenic Activity ◽  
Current State ◽  
Structure Activity ◽  
Carcinogenic Potential

AbstractThe purpose of this paper is to report on an expert system in design that screens for potential hazards from environmental chemicals on the basis of structure-activity relationships in the study of chemical carcinogenesis, particularly with respect to analyzing the current state of known structural information about chemical carcinogens and predicting the possible carcinogenicity of untested chemicals. The structure-activity tree serves as an index of known chemical structure features associated with carcinogenic activity. The basic units of the tree are the principal recognized classes of chemical carcinogens that are subdivided into subclasses known as nodes according to specific structural features that may reflect differences in carcinogenic potential among chemicals in the class. An analysis of a computerized data base of known carcinogens (knowledge base) is proposed using the structure-activity tree in order to test the validity of the tree as a classification scheme (inference engine).

scholarly journals Host Cell Restriction Factors of Bunyaviruses and Viral Countermeasures

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 784
Author(s):  
Solène Lerolle ◽  
Natalia Freitas ◽  
François-Loïc Cosset ◽  
Vincent Legros
Keyword(s):  
Host Cell ◽  
Viral Entry ◽  
Current Knowledge ◽  
Restriction Factors ◽  
Antiviral State ◽  
Cellular Factors ◽  
Pathogenic Viruses ◽  
Genome Transcription ◽  
Infected Cells ◽  
Molecular Patterns

The Bunyavirales order comprises more than 500 viruses (generally defined as bunyaviruses) classified into 12 families. Some of these are highly pathogenic viruses infecting different hosts, including humans, mammals, reptiles, arthropods, birds, and/or plants. Host cell sensing of infection activates the innate immune system that aims at inhibiting viral replication and propagation. Upon recognition of pathogen-associated molecular patterns (PAMPs) by cellular pattern recognition receptors (PRRs), numerous signaling cascades are activated, leading to the production of interferons (IFNs). IFNs act in an autocrine and paracrine manner to establish an antiviral state by inducing the expression of hundreds of IFN-stimulated genes (ISGs). Some of these ISGs are known to restrict bunyavirus infection. Along with other constitutively expressed host cellular factors with antiviral activity, these proteins (hereafter referred to as “restriction factors”) target different steps of the viral cycle, including viral entry, genome transcription and replication, and virion egress. In reaction to this, bunyaviruses have developed strategies to circumvent this antiviral response, by avoiding cellular recognition of PAMPs, inhibiting IFN production or interfering with the IFN-mediated response. Herein, we review the current knowledge on host cellular factors that were shown to restrict infections by bunyaviruses. Moreover, we focus on the strategies developed by bunyaviruses in order to escape the antiviral state developed by the infected cells.

scholarly journals Significance of thiol-disulfide balance in SARS-CoV-2 infection

2021 ◽  
Vol 72 (3) ◽  
pp. 30-36
Author(s):  
Tatjana Simić
Keyword(s):  
Cell Surface ◽  
Host Cell ◽  
Protein Interactions ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Alkylating Agents ◽  
Protein S ◽  
Protein Protein Interactions ◽  
Virus Surface ◽  
Host Cell Surface

Studies of the molecular mechanisms regarding interaction of different viruses with receptors on the host cell surface have shown that the viral entry depends on the specific relationship between free thiol (SH) groups and disulfides on the virus surface, as well as the thiol disulfide balance on the host cell surface. The presence of oxidizing compounds or alkylating agents, which disturb the thiol-disulfide balance on the surface of the virus, can also affect its infectious potential. Disturbed thiol-disulfide balance may also influence protein-protein interactions between SARS-CoV-2 protein S and ACE2 receptors of the host cell. This review presents the basic mechanisms of maintaining intracellular and extracellular thiol disulfide balance and previous experimental and clinical evidence in favor of impaired balance in SARS-CoV-2 infection. Besides, the results of the clinical application or experimental analysis of compounds that induce changes in the thiol disulfide balance towards reduction of disulfide bridges in proteins of interest in COVID-19 infection are presented.

scholarly journals Shared paramyxoviral glycoprotein architecture is adapted for diverse attachment strategies

2010 ◽  
Vol 38 (5) ◽  
pp. 1349-1355 ◽  
Author(s):  
Thomas A. Bowden ◽  
Max Crispin ◽  
E. Yvonne Jones ◽  
David I. Stuart
Keyword(s):  
Cell Surface ◽  
Viral Entry ◽  
Cell Attachment ◽  
Structural Information ◽  
Cell Receptor ◽  
Specific Protein ◽  
Cell Surface Receptors ◽  
Surface Receptors ◽  
Entry Inhibitors ◽  
Animal Pathogens

Members within the paramyxovirus subfamily Paramyxovirinae constitute a large number of highly virulent human and animal pathogens. The glycoproteins present on these viruses are responsible for mediating host cell attachment and fusion and are key targets for the design of antiviral entry inhibitors. In the present review, we discuss recent structural studies which have led to a better understanding of the various mechanisms by which different paramyxoviruses use their attachment glycoproteins to hijack specific protein and glycan cell-surface receptors to facilitate viral entry. It is observed that the paramyxovirus attachment glycoprotein consists of a conserved overall structure which includes an N-terminal six-bladed β-propeller domain which is responsible for cell receptor binding. Crystal structures of this domain from different biomedically important paramyxoviruses, including measles, Nipah, Hendra, Newcastle disease and parainfluenza viruses, alone and in complex with their functional cell-surface receptors, demonstrate three contrasting mechanisms of receptor engagement that paramyxoviruses have evolved to confer discreet protein- and glycan-receptor specificity. This structural information highlights the adaptability of the paramyxovirus attachment glycoprotein surface and the potential for the emergence of new and potentially harmful viruses in human hosts.

scholarly journals HIV Cell Fusion Assay

2013 ◽  
Vol 19 (1) ◽  
pp. 108-118 ◽  
Author(s):  
Elizabeth B. Smith ◽  
Robert A. Ogert ◽  
David Pechter ◽  
Artjohn Villafania ◽  
Susan J. Abbondanzo ◽  
...  
Keyword(s):  
Host Cell ◽  
Cell Fusion ◽  
Chemokine Receptor ◽  
Viral Entry ◽  
Envelope Glycoprotein ◽  
Laser Scanning ◽  
Viral Envelope ◽  
Fusion Event ◽  
Cxcr4 Signaling ◽  
Hiv Entry

The health and disease-related biology of the CXCR4 chemokine receptor presents the challenge of finding a small molecule that can bind CXCR4 and block T-cell tropic human immunodeficiency virus type 1 (HIV-1) cell entry, while preserving the ability of CXCR4 to respond to its native ligand, CXCL12. HIV entry into the host cell involves the interaction of the viral envelope glycoprotein gp120 binding to CD4, followed by a rearrangement in gp120, and subsequent interaction with the chemokine receptor CXCR4 or CCR5. These initial events can be re-created in a cell fusion assay that represents a surrogate system, mimicking the early stages of viral entry via these host cell receptors. In the current study, a T-tropic HIV cell fusion assay was established using U2OS cells expressing the envelope glycoprotein gp160 from the T-tropic HIV NL4-3 and HeLa cells expressing CD4 and CXCR4. Detection of the cell fusion event was based on a Gal4/VP16-activated β-lactamase signal and was measured by automated microscopy or laser scanning plate cytometry. Changes in morphology associated with cell fusion were combined with β-lactamase activity to generate results with robust assay statistics in both 384-well and 1536-well plates. Compounds were subsequently characterized by CXCR4 signaling assays to eliminate functional antagonists and allow the identification of a function-sparing HIV entry inhibitor.

Metainflammation in COVID-19

2022 ◽  
Vol 22 ◽  
Author(s):  
Mojtaba Bakhtiari ◽  
Kamyar Asadipooya
Keyword(s):  
Cell Membrane ◽  
Viral Entry ◽  
Virus Entry ◽  
Host Cells ◽  
Elderly Men ◽  
Virus Binding ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Beneficial Effects ◽  
Binding Capability

Abstract: A new coronavirus pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2], has been on the rise. This virus is fatal for broad groups of populations, including elderly, men, and patients with comorbidities among which obesity is a possible risk factor. The pathophysiologic connections between obesity/metainflammation and COVID-19 may be directly related to increasing soluble ACE2 (angiotensin-converting enzyme 2] levels which potentiates the viral entrance into the host cells, or indirectly related to dysregulation of immune system, microvascular injury and hypercoagulability. The SARS-CoV-2 S-glycoprotein interacts mainly with ACE2 or possibly DDP4 receptors to enter into the host cells. The host proteases, especially TMPRSS2 (transmembrane protease serine 2], support the fusion process and virus entry. While membranous ACE2 is considered a port of entry to the cell for SARS-CoV-2, it seems that soluble ACE2 retains its virus binding capability and enhances its entry into the cells. Interestingly, ACE2 on cell membrane may have protective roles by diminishing cytokine storm-related injuries to the organs. Applying medications that can reduce soluble ACE2 levels, antagonizing TMPRSS2 or blocking DDP4 can improve the outcomes of COVID-19. Metformin and statins through immunomodulatory activities, Orlistat by reducing viral replication, and thiazolidinediones by upregulating ACE2 expression have potential beneficial effects against COVID-19. However, the combination of dipeptidyl peptidase-4 (DDP4] inhibitors and spironolactone/eplerenone seems to be more effective by reducing soluble ACE2 level, antagonizing TMPRSS2, maintaining ACE2 on cell membrane and reducing risk of viral entry into the cells.

scholarly journals Monitoring Viral Entry in Real-Time Using a Luciferase Recombinant Vesicular Stomatitis Virus Producing SARS-CoV-2, EBOV, LASV, CHIKV, and VSV Glycoproteins

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1457
Author(s):  
Maria Fernanda Lay Mendoza ◽  
Marissa Danielle Acciani ◽  
Courtney Nina Levit ◽  
Christopher Santa Maria ◽  
Melinda Ann Brindley
Keyword(s):  
Real Time ◽  
Vesicular Stomatitis Virus ◽  
Viral Entry ◽  
Cell Surface Receptor ◽  
Enveloped Virus ◽  
Glycoprotein G ◽  
Viral Glycoproteins ◽  
Surface Receptor ◽  
Vesicular Stomatitis ◽  
Time Required

Viral entry is the first stage in the virus replication cycle and, for enveloped viruses, is mediated by virally encoded glycoproteins. Viral glycoproteins have different receptor affinities and triggering mechanisms. We employed vesicular stomatitis virus (VSV), a BSL-2 enveloped virus that can incorporate non-native glycoproteins, to examine the entry efficiencies of diverse viral glycoproteins. To compare the glycoprotein-mediated entry efficiencies of VSV glycoprotein (G), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S), Ebola (EBOV) glycoprotein (GP), Lassa (LASV) GP, and Chikungunya (CHIKV) envelope (E) protein, we produced recombinant VSV (rVSV) viruses that produce the five glycoproteins. The rVSV virions encoded a nano luciferase (NLucP) reporter gene fused to a destabilization domain (PEST), which we used in combination with the live-cell substrate EndurazineTM to monitor viral entry kinetics in real time. Our data indicate that rVSV particles with glycoproteins that require more post-internalization priming typically demonstrate delayed entry in comparison to VSV G. In addition to determining the time required for each virus to complete entry, we also used our system to evaluate viral cell surface receptor preferences, monitor fusion, and elucidate endocytosis mechanisms. This system can be rapidly employed to examine diverse viral glycoproteins and their entry requirements.

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