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Modified cyclodextrins as broad-spectrum antivirals.
- Source :
-
Science advances [Sci Adv] 2020 Jan 29; Vol. 6 (5), pp. eaax9318. Date of Electronic Publication: 2020 Jan 29 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- 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.<br /> (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).)
- Subjects :
- Acyclovir chemistry
Acyclovir pharmacology
Animals
Antiviral Agents chemical synthesis
Antiviral Agents chemistry
Antiviral Agents pharmacology
Cyclodextrins chemical synthesis
Cyclodextrins chemistry
Female
Gold chemistry
Heparitin Sulfate chemistry
Heparitin Sulfate pharmacology
Herpesvirus 1, Human pathogenicity
Herpesvirus 2, Human pathogenicity
Humans
Metal Nanoparticles chemistry
Mice
Simplexvirus drug effects
Simplexvirus pathogenicity
Virus Diseases virology
Zika Virus drug effects
Zika Virus pathogenicity
Cyclodextrins pharmacology
Herpesvirus 1, Human drug effects
Herpesvirus 2, Human drug effects
Virus Diseases drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2375-2548
- Volume :
- 6
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Science advances
- Publication Type :
- Academic Journal
- Accession number :
- 32064341
- Full Text :
- https://doi.org/10.1126/sciadv.aax9318