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Modified cyclodextrins as broad-spectrum antivirals

Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanop...

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Autores principales: Jones, Samuel T., Cagno, Valeria, Janeček, Matej, Ortiz, Daniel, Gasilova, Natalia, Piret, Jocelyne, Gasbarri, Matteo, Constant, David A., Han, Yanxiao, Vuković, Lela, Král, Petr, Kaiser, Laurent, Huang, Song, Constant, Samuel, Kirkegaard, Karla, Boivin, Guy, Stellacci, Francesco, Tapparel, Caroline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989148/
https://www.ncbi.nlm.nih.gov/pubmed/32064341
http://dx.doi.org/10.1126/sciadv.aax9318
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author Jones, Samuel T.
Cagno, Valeria
Janeček, Matej
Ortiz, Daniel
Gasilova, Natalia
Piret, Jocelyne
Gasbarri, Matteo
Constant, David A.
Han, Yanxiao
Vuković, Lela
Král, Petr
Kaiser, Laurent
Huang, Song
Constant, Samuel
Kirkegaard, Karla
Boivin, Guy
Stellacci, Francesco
Tapparel, Caroline
author_facet Jones, Samuel T.
Cagno, Valeria
Janeček, Matej
Ortiz, Daniel
Gasilova, Natalia
Piret, Jocelyne
Gasbarri, Matteo
Constant, David A.
Han, Yanxiao
Vuković, Lela
Král, Petr
Kaiser, Laurent
Huang, Song
Constant, Samuel
Kirkegaard, Karla
Boivin, Guy
Stellacci, Francesco
Tapparel, Caroline
author_sort Jones, Samuel T.
collection PubMed
description Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.
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spelling pubmed-69891482020-02-14 Modified cyclodextrins as broad-spectrum antivirals Jones, Samuel T. Cagno, Valeria Janeček, Matej Ortiz, Daniel Gasilova, Natalia Piret, Jocelyne Gasbarri, Matteo Constant, David A. Han, Yanxiao Vuković, Lela Král, Petr Kaiser, Laurent Huang, Song Constant, Samuel Kirkegaard, Karla Boivin, Guy Stellacci, Francesco Tapparel, Caroline Sci Adv Research Articles Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails. American Association for the Advancement of Science 2020-01-29 /pmc/articles/PMC6989148/ /pubmed/32064341 http://dx.doi.org/10.1126/sciadv.aax9318 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Jones, Samuel T.
Cagno, Valeria
Janeček, Matej
Ortiz, Daniel
Gasilova, Natalia
Piret, Jocelyne
Gasbarri, Matteo
Constant, David A.
Han, Yanxiao
Vuković, Lela
Král, Petr
Kaiser, Laurent
Huang, Song
Constant, Samuel
Kirkegaard, Karla
Boivin, Guy
Stellacci, Francesco
Tapparel, Caroline
Modified cyclodextrins as broad-spectrum antivirals
title Modified cyclodextrins as broad-spectrum antivirals
title_full Modified cyclodextrins as broad-spectrum antivirals
title_fullStr Modified cyclodextrins as broad-spectrum antivirals
title_full_unstemmed Modified cyclodextrins as broad-spectrum antivirals
title_short Modified cyclodextrins as broad-spectrum antivirals
title_sort modified cyclodextrins as broad-spectrum antivirals
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989148/
https://www.ncbi.nlm.nih.gov/pubmed/32064341
http://dx.doi.org/10.1126/sciadv.aax9318
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