Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets Vir

[Snowy Owl]

Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets Viral Attachment to Cells

Journal of Virology, December 2006, p. 11960-11967, Vol. 80, No. 24
0022-538X/06/$08.00+0 doi:10.1128/JVI.01678-06
Copyright ? 2006, American Society for Microbiology. All Rights Reserved.

Jeremy C. Jones,<SUP>1</SUP> Elizabeth A. Turpin,<SUP>1</SUP><SUP>,

</SUP> Hermann Bultmann,<SUP>2</SUP> Curtis R. Brandt,<SUP>1</SUP><SUP>,2</SUP> and Stacey Schultz-Cherry<SUP>1</SUP><SUP>*</SUP> ​

Departments of Medical Microbiology and Immunology,<SUP>1</SUP> Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin 53706<SUP>2</SUP>

Received 3 August 2006/ Accepted 12 September 2006

http://jvi.asm.org/cgi/content/abstract/80/24/11960
​

Influenza A viruses continue to cause widespread morbidity and<SUP> </SUP>mortality. There is an added concern that the highly pathogenic<SUP> </SUP>H5N1 influenza A viruses, currently found throughout many parts<SUP> </SUP>of the world, represent a serious public health threat and may<SUP> </SUP>result in a pandemic.

Intervention strategies to halt an influenza<SUP> </SUP>epidemic or pandemic are a high priority, with an emphasis on<SUP> </SUP>vaccines and antiviral drugs.

In these studies, we demonstrate<SUP> </SUP>that a 20-amino-acid peptide (EB, for entry blocker) derived<SUP> </SUP>from the signal sequence of fibroblast growth factor 4 exhibits<SUP> </SUP>broad-spectrum antiviral activity against influenza viruses<SUP> </SUP>including the H5N1 subtype in vitro.

The EB peptide was protective<SUP> </SUP>in vivo, even when administered postinfection.

Mechanistically,<SUP> </SUP>the EB peptide inhibits the attachment to the cellular receptor,<SUP> </SUP>preventing infection. Further studies demonstrated that the<SUP> </SUP>EB peptide specifically binds to the viral hemagglutinin protein.<SUP> </SUP>This novel peptide has potential value as a reagent to study<SUP> </SUP>virus attachment and as a future therapeutic.<SUP> </SUP>​

 

[Linda]

Re: Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets

Re: Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets

Ok, This might sound silly but could eating rainbow trout help block the H5N1 virus?

http://cat.inist.fr/?aModele=afficheN&cpsidt=14927622

Titre du document / Document title
Specific cell surface binding sites shared by human Pro-IGF-I Eb-peptides and rainbow trout Pro-IGF-I Ea-4-peptide
Auteur(s) / Author(s)
KUO Ya-Huei ; CHEN Thomas T. ;
R?sum? / Abstract
Human pro-IGF-I Eb-peptide (hEb) and rainbow trout pro-IGF-I Ea-4-peptide (rtEa-4) have recently been shown to share unique biological activities [Gen. Comp. Endocrinol. 126 (2002) 342; Cell. Exp. Cell. Res. 280 (2002) 75]. To further understand the action mechanism of these proteins, we studied the binding properties of hEb-peptide and rtEa-4-peptide to intact human neuroblastoma cells (SK-N-F1) and membrane preparations. Human Eb-peptide and rtEa-4-peptide bind to a high-affinity binding site with an apparent dissociation constant of 3.2 ′ 1.9 ? 10[-][1] and 2.9 ′ 1.89 ? 10[-][1][1] M, respectively. Homologous displacement assay demonstrated the presence of a second binding site with an IC[5][0] of 4.8 ′ 2.6 x 10[-][6]M for hEb-peptide and 2.1 ′ 0.6 x 10[-][6] M for rtEa-4-peptide, respectively. Competition assays showed that hEb-peptide and rtEa-4-peptide shared common binding sites, distinct from those for IGF-I and insulin. In addition, chemical cross-linking studies revealed two specific binding complexes. Our findings support the notion that the initial step of pro-IGF-I E-peptide action is mediated through the interaction with conserved and specific putative membrane receptors on neuroblastoma cells.
Revue / Journal Title
General and comparative endocrinology (Gen. comp. endocrinol.) ISSN 0016-6480 CODEN GCENA5
Source / Source
2003, vol. 132, no2, pp. 231-240 [10 page(s) (article)]
Langue / Language
Anglais
Editeur / Publisher
Academic Press, San Diego, CA, ETATS-UNIS (1961) (Revue)


Localisation / Location
INIST-CNRS, Cote INIST : 1625, 35400011859726.0070

Copyright 2006 INIST-CNRS. All rights reserved
Toute reproduction ou diffusion m?me partielle, par quelque proc?d? ou sur tout support que ce soit, ne pourra ?tre faite sans l'accord pr?alable ?crit de l'INIST-CNRS.
No part of these records may be reproduced of distributed, in any form or by any means, without the prior written permission of INIST-CNRS.
N? notice refdoc (ud4) : 14927622

Envoyer le lien de cette r?f?rence Imprimer / Print Retour / Back

 

[Mingus]

Re: Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets

Re: Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets

No Linda, this peptide was called like that to mean "Entry Blocker" as a simple nick-name but it is a part of the "Fibroblast growth factor 4 precursor (FGF-4) signal peptide.

Those two letters in that other peptide are a pure coincidence.

A signal peptide is a "tag" include in a immature protein when first synthetises by a cell to direct it to the appropriate part of the cell where it could mature to it's final form. It is then removed.

By the research process the discoverd that this one haved a cell penetrating capability. It is part of a wider family called CPP ( cell penetrating peptides ).

In the latests developpement of the pharmaceutical research, they try to use theses peptides linked to bigger molecules to help thoses molecule enter the cell. They then realised that some of theses CPP haved antimicrobials activities of their own.

This one called EB, was first tested for it's anti-herpes simplex activities & was proved to be potent as therapeutic as well as prophylactic because it it beleive to protect cells previously to the virus contact.

This last article highlight also his anti-influenza activities.

This new class of antivirals show us big promises as long a they showed very low toxicity when first tested.

The trick will be to get them a longer half-life.

( I must admit I read long about them...)

 

[Mingus]

Re: Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets

Re: Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets

First toxicity study about the EB peptide. ( they used it as a ophtalmic droplet to treat herpes-simplex caused keratitis. It showed no toxicity.


http://www.liebertonline.com/doi/abs...op.2006.22.279


Journal of Ocular Pharmacology and Therapeutics
Corneal Toxicity of Cell-Penetrating Peptides That Inhibit Herpes simplex Virus Entry
Aug 2006, Vol. 22, No. 4 : 279 -289
<!-- End title of page and review --><!-- Start full text content --><!-- abstract content -->

Radeekorn Akkarawongsa Program in Cell and Molecular Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Amy E. Cullinan Microbiology Doctoral Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Andrew Zinkel Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Joshua Clarin Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Curtis R. Brandt Department of Ophthalmology and Visual Sciences, and Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Cell-penetrating peptides (CPPs) inhibit Herpes simplex virus entry at low micromolar concentrations and may be useful either as prophylactic or therapeutic agents for herpetic keratitis. The aim of this study was to assess the in vitro and in vivo toxicity of three CPPs?EB, TAT-C, and HOM (penetratin)?for the cornea. Incubation of primary (HK320) or immortalized (THK320) human keratocytes with the EB peptide (up to 100 ?M), bHOMd (up to 200 ?M), or TAT-C (up to 400 ?M) resulted in no evidence of toxicity using a formazan dye-reduction assay. Similar results were obtained with a human trabecular meshwork cell line (TM-1), primary human foreskin fibroblasts (DP-9), Vero, and HeLa cells with EB and TATC. The bHOMd peptide showed some toxicity in Vero and HeLa cells, with CC₅₀ values of 70 and 93 ?M, respectively. The EB peptide did not inhibit macromolecular synthesis in Vero cells at concentrations below 150 ?M, although cell proliferation was blocked at concentrations of EB above 50 ?M. In vivo toxicity was assessed by applying peptides in Dulbecco's modified Eagle's medium to the cornea 4 times daily for 7 d. At concentrations 1000 times the IC₅₀ values, the EB and bHOM peptides showed no toxicity, whereas TAT-C caused some mild eyelid swelling. Some slight epithelial cell sloughing was seen with the bKLA peptide in vivo. These results suggest that these CPPs?and EB in particular?have a favorable toxicity profile, and that further development is warranted.

 

[AlaskaDenise]

Re: Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets Vir

Welcome to the forum Linda.

I'm still eating Rainbow Trout - love them.

.

 

[Linda]

Re: Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets

Re: Inhibition of Influenza Virus Infection by a Novel Antiviral Peptide That Targets

Thanks for the answers and the welcome. I've actually been lurking here off and on for a long time :tiphat: nice to meet you all.