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Modified cyclodextrins as broad-spectrum antivirals.

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.

SUBMITTER: Jones ST

PROVIDER: S-EPMC6989148 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Modified cyclodextrins as broad-spectrum antivirals.

Jones Samuel T ST Cagno Valeria V Janeček Matej M Ortiz Daniel D Gasilova Natalia N Piret Jocelyne J Gasbarri Matteo M Constant David A DA Han Yanxiao Y Vuković Lela L Král Petr P Kaiser Laurent L Huang Song S Constant Samuel S Kirkegaard Karla K Boivin Guy G Stellacci Francesco F Tapparel Caroline C

Science advances 20200129 5

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 ...[more]

PMID: 32064341

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Modified cyclodextrins as broad-spectrum antivirals.

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Modified cyclodextrins as broad-spectrum antivirals.

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