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Nat Mater. 2018 Feb;17(2):195-203. doi: 10.1038/nmat5053. Epub 2017 Dec 18.

Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism.

Author information

1
Dipartimento di Scienze Cliniche e Biologiche, Univerisità degli Studi di Torino, Orbassano, Italy.
2
Institute of Materials, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
3
Faculty of Medicine of Geneva, Department of Microbiology and Molecular medicine, Geneva, Switzerland.
4
IFOM - FIRC Institute of Molecular Oncology, IFOM-IEO Campus, Milan, Italy.
5
CIC biomaGUNE Soft Matter Nanotechnology Group San Sebastian-Donostia, 20014 Donastia San Sebastián, Spain.
6
Fondazione Centro Europeo Nanomedicina (CEN), Milan, Italy.
7
VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France.
8
Jones Lab, School of Materials, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
9
Istituto per la Protezione Sostenibile delle Piante, CNR, Torino, Italy.
10
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
11
Department of Chemistry, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
12
Fondazione IRCCS Istituto Neurologico "Carlo Besta", IFOM-IEO Campus, Milan, Italy.
13
UMR INSERM U1173 I2, UFR des Sciences de la Santé Simone Veil-UVSQ, Montigny-Le-Bretonneux, France.
14
AP-HP, Laboratoire de Microbiologie, Hôpital Ambroise Paré, 92104 Boulogne-Billancourt, France.
15
Geneva University Hospitals, Infectious Diseases Divisions, Geneva, Switzerland.
16
Department of Chemistry, University of Texas at El Paso, El Paso, Texas 79968, USA.
17
Department of Physics and Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, USA.
18
IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
19
Interfaculty Bioengineering Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Abstract

Viral infections kill millions yearly. Available antiviral drugs are virus-specific and active against a limited panel of human pathogens. There are broad-spectrum substances that prevent the first step of virus-cell interaction by mimicking heparan sulfate proteoglycans (HSPG), the highly conserved target of viral attachment ligands (VALs). The reversible binding mechanism prevents their use as a drug, because, upon dilution, the inhibition is lost. Known VALs are made of closely packed repeating units, but the aforementioned substances are able to bind only a few of them. We designed antiviral nanoparticles with long and flexible linkers mimicking HSPG, allowing for effective viral association with a binding that we simulate to be strong and multivalent to the VAL repeating units, generating forces (∼190 pN) that eventually lead to irreversible viral deformation. Virucidal assays, electron microscopy images, and molecular dynamics simulations support the proposed mechanism.  These particles show no cytotoxicity, and in vitro nanomolar irreversible activity against herpes simplex virus (HSV), human papilloma virus, respiratory syncytial virus (RSV), dengue and lenti virus. They are active ex vivo in human cervicovaginal histocultures infected by HSV-2 and in vivo in mice infected with RSV.

Comment in

PMID:
29251725
DOI:
10.1038/nmat5053
[Indexed for MEDLINE]
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