Faculty Opinions recommendation of Mechanisms of immunomodulation by mammalian and viral decoy receptors: insights from structures.

2018 ◽  
Author(s):  
Antonio Alcami
Keyword(s):  
Decoy Receptors

scholarly journals An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants

2021 ◽  
Vol 7 (8) ◽  
pp. eabf1738 ◽  
Author(s):  
Kui K. Chan ◽  
Timothy J. C. Tan ◽  
Krishna K. Narayanan ◽  
Erik Procko
Keyword(s):  
In Vitro Selection ◽  
Protein S ◽  
Saturation Mutagenesis ◽  
Wild Type ◽  
Host Cell Membrane ◽  
Decoy Receptor ◽  
Decoy Receptors ◽  
Binding Surface ◽  
Type Receptor

The spike S of SARS-CoV-2 recognizes ACE2 on the host cell membrane to initiate entry. Soluble decoy receptors, in which the ACE2 ectodomain is engineered to block S with high affinity, potently neutralize infection and, because of close similarity with the natural receptor, hold out the promise of being broadly active against virus variants without opportunity for escape. Here, we directly test this hypothesis. We find that an engineered decoy receptor, sACE22.v2.4, tightly binds S of SARS-associated viruses from humans and bats, despite the ACE2-binding surface being a region of high diversity. Saturation mutagenesis of the receptor-binding domain followed by in vitro selection, with wild-type ACE2 and the engineered decoy competing for binding sites, failed to find S mutants that discriminate in favor of the wild-type receptor. We conclude that resistance to engineered decoys will be rare and that decoys may be active against future outbreaks of SARS-associated betacoronaviruses.

Biochemical mechanisms that interact with membrane-associated IL-1 RII (60-kDa decoy) receptors in populations of adherent macrophages and vascular endothelium

2001 ◽  
Vol 13 (10) ◽  
pp. 765-776 ◽  
Author(s):  
Cody Coyne ◽  
Jeff Baravick ◽  
Trey Howell ◽  
Erica Baravick ◽  
Carla Willetto ◽  
...  
Keyword(s):  
Vascular Endothelium ◽  
Decoy Receptors ◽  
Biochemical Mechanisms

scholarly journals Epigenetic inactivation of TRAIL decoy receptors at 8p12-21.3 commonly deleted region confers sensitivity to Apo2L/trail-Cisplatin combination therapy in cervical cancer

2015 ◽  
Vol 55 (2) ◽  
pp. 177-189 ◽  
Author(s):  
Gopeshwar Narayan ◽  
Dongxu Xie ◽  
Ganchimeg Ishdorj ◽  
Luigi Scotto ◽  
Mahesh Mansukhani ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Combination Therapy ◽  
Epigenetic Inactivation ◽  
Decoy Receptors

Decoy receptors thwart B cells

Nature ◽  
2000 ◽  
Vol 404 (6781) ◽  
pp. 949-950 ◽  
Author(s):  
Carl F. Ware
Keyword(s):  
B Cells ◽  
Decoy Receptors

Virus-encoded cytokine and chemokine decoy receptors

2020 ◽  
Vol 66 ◽  
pp. 50-56 ◽  
Author(s):  
Bruno Hernaez ◽  
Antonio Alcamí
Keyword(s):  
Decoy Receptors

scholarly journals Experimental Models in Neovascular Age Related Macular Degeneration

2020 ◽  
Vol 21 (13) ◽  
pp. 4627
Author(s):  
Olivia Rastoin ◽  
Gilles Pagès ◽  
Maeva Dufies
Keyword(s):  
Macular Degeneration ◽  
Experimental Models ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
In Vivo Models ◽  
Age Related ◽  
Decoy Receptors ◽  
Endothelial Growth Factor

Neovascular age-related macular degeneration (vAMD), characterized by the neo-vascularization of the retro-foveolar choroid, leads to blindness within few years. This disease depends on angiogenesis mediated by the vascular endothelial growth factor A (VEGF) and to inflammation. The only available treatments consist of monthly intravitreal injections of antibodies directed against VEGF or VEGF/VEGFB/PlGF decoy receptors. Despite their relative efficacy, these drugs only delay progression to blindness and 30% of the patients are insensitive to these treatments. Hence, new therapeutic strategies are urgently needed. Experimental models of vAMD are essential to screen different innovative therapeutics. The currently used in vitro and in vivo models in ophthalmic translational research and their relevance are discussed in this review.

scholarly journals Decoy Receptor Interactions as Novel Drug Targets against EKC-Causing Human Adenovirus

Viruses ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 242 ◽  
Author(s):  
Naresh Chandra ◽  
Lars Frängsmyr ◽  
Niklas Arnberg
Keyword(s):  
Drug Targets ◽  
Antiviral Drug ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Antiviral Effect ◽  
Epidemic Keratoconjunctivitis ◽  
Virus Binding ◽  
Decoy Receptor ◽  
Decoy Receptors ◽  
Approved Drugs

Epidemic keratoconjunctivitis (EKC) is a severe ocular disease and can lead to visual impairment. Human adenovirus type-37 (HAdV-D37) is one of the major causative agents of EKC and uses sialic acid (SA)-containing glycans as cellular receptors. Currently, there are no approved antivirals available for the treatment of EKC. Recently, we have reported that sulfated glycosaminoglycans (GAGs) bind to HAdV-D37 via the fiber knob (FK) domain of the viral fiber protein and function as decoy receptors. Based on this finding, we speculated that GAG-mimetics may act as artificial decoy receptors and inhibit HAdV-D37 infection. Repurposing of approved drugs to identify new antivirals has drawn great attention in recent years. Here, we report the antiviral effect of suramin, a WHO-approved drug and a widely known GAG-mimetic, against HAdV-D37. Commercially available suramin analogs also show antiviral effects against HAdV-D37. We demonstrate that suramin exerts its antiviral activity by inhibiting the attachment of HAdV-D37 to cells. We also reveal that the antiviral effect of suramin is HAdV species-specific. Collectively, in this proof of concept study, we demonstrate for the first time that virus binding to a decoy receptor constitutes a novel and an unexplored target for antiviral drug development.

scholarly journals Addition of a Viral Immunomodulatory Domain to Etanercept Generates a Bifunctional Chemokine and TNF Inhibitor

2019 ◽  
Vol 9 (1) ◽  
pp. 25 ◽  
Author(s):  
Alí Alejo ◽  
Carolina Sánchez ◽  
Sylvie Amu ◽  
Padraic G. Fallon ◽  
Antonio Alcamí
Keyword(s):  
Inflammatory Responses ◽  
Protein A ◽  
Disease Model ◽  
Tnf Inhibitor ◽  
Critical Determinant ◽  
Viral Spread ◽  
Inflammatory Conditions ◽  
Decoy Receptors ◽  
Bifunctional Inhibitor

The inhibition of tumor necrosis factor (TNF) through the use of either antibodies or soluble receptors is a highly effective strategy for the clinical control of chronic inflammatory conditions such as rheumatoid arthritis. Different viruses have similarly exploited this concept by expressing a set of specifically tailored secreted TNF decoy receptors to block host inflammatory responses. Poxviruses have been shown to encode at least two distinct molecules, termed Cytokine response modifier D (CrmD) and CrmB, in which a TNF inhibitor is combined with a chemokine inhibitor on the same molecule. The ectromelia virus CrmD protein was found to be a critical determinant of virulence in vivo, being able to control local inflammation to allow further viral spread and the establishment of a lethal infection. Strikingly, both the TNF and the chemokine inhibitory domains are required for the full activity of CrmD, suggesting a model in which inhibition of TNF is supported by the concomitant blockade of a reduced set of chemokines. Inspired by this model, we reasoned that a similar strategy could be applied to modify the clinically used human TNF receptor (etanercept), producing a generation of novel, more effective therapeutic agents. Here we show the analysis of a set of fusion proteins derived from etanercept by addition of a viral chemokine-binding protein. A bifunctional inhibitor capable of binding to and blocking the activity of TNF as well as a set of chemokines is generated that is active in the prevention of arthritis in a murine disease model.

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