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.
Original language | English |
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Article number | eaax9318 |
Journal | Science Advances |
Volume | 6 |
Issue number | 5 |
DOIs | |
Publication status | Published - 29 Jan 2020 |
Bibliographical note
Funding Information:S.T.J. was supported by Dame Kathleen Ollerenshaw Fellowship. V.C. was supported by Firmenich Foundation for EPFL-Stanford Exchange. J.P. and G.B. were financed by the Canadian Institutes of Health Research (grant no. 148361 to G.B.). L.V. was supported by the NIAID of the NIH under award number R03AI142553. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We thank the reviewers for their useful feedback on additional experiments especially the DNase experiment that strengthened the message in our manuscript. The work was supported by the Leenaards Foundation (grant 4390 to C.T. and F.S.) and the Swiss National Science Foundation (via a Sinergia grant CRSII5-180323 to F.S. and C.T.), and the National Center of Competence in Research (NCCR) Bio-Inspired Materials that supported M.G.
Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved.
ASJC Scopus subject areas
- General