Broad-spectrum non-toxic antiviral nanoparticles with a virucidal inhibition mechanism
Valeria Cagno
(1, 2, 3)
,
Patrizia Andreozzi
(4, 5)
,
Marco d'Alicarnasso
(6)
,
Paulo Jacob Silva
(2)
,
Marie Mueller
(2)
,
Marie Galloux
(7, 8)
,
Ronan Le Goffic
(7, 8)
,
Samuel T Jones
(9, 2)
,
Marta Vallino
(10)
,
Jan Hodek
(11)
,
Jan Weber
(11)
,
Soumyo Sen
(12)
,
Emma-Rose Janeček
(2)
,
Ahmet Bekdemir
(2)
,
Barbara Sanavio
(13)
,
Chiara Martinelli
(4)
,
Manuela Donalisio
(1)
,
Marie-Anne Rameix Welti
(14, 15)
,
Jean Francois Eleouet
(7, 8)
,
Yanxiao Han
(12)
,
Laurent Kaiser
(16)
,
Lela Vukovic
(17)
,
Caroline Tapparel
(3, 16)
,
Silke Krol
(18, 19)
,
David Lembo
(1)
,
Francesco Stellacci
(2, 20)
1
UNITO -
Università degli studi di Torino = University of Turin
2 Institute of Materials
3 UNIGE - Université de Genève = University of Geneva
4 IFOM - FIRC
5 CIC biomaGUNE - Centro de Investigación Cooperativa en Biomateriales
6 Fondazione CEN
7 VIM (UR 0892) - Unité de recherche Virologie et Immunologie Moléculaires
8 Université Paris Saclay (COmUE)
9 University of Manchester [Manchester]
10 IPSP - CNR Istituto per la Protezione Sostenibile delle Piante [Torino, Italia]
11 CAS - Czech Academy of Sciences [Prague]
12 University of Illinois
13 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
14 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
15 2I - Infection et inflammation
16 HUG - Hôpitaux Universitaires de Genève
17 University of Texas
18 IRCCS Ist Tumori Giovanni Paolo II, Bari, Italy
19 Fdn IRCCS Ist Neurol Carlo Besta, IFOM IEO Campus, Milan, Italy
20 EPFL - Ecole Polytechnique Fédérale de Lausanne
2 Institute of Materials
3 UNIGE - Université de Genève = University of Geneva
4 IFOM - FIRC
5 CIC biomaGUNE - Centro de Investigación Cooperativa en Biomateriales
6 Fondazione CEN
7 VIM (UR 0892) - Unité de recherche Virologie et Immunologie Moléculaires
8 Université Paris Saclay (COmUE)
9 University of Manchester [Manchester]
10 IPSP - CNR Istituto per la Protezione Sostenibile delle Piante [Torino, Italia]
11 CAS - Czech Academy of Sciences [Prague]
12 University of Illinois
13 Fondazione IRCCS Istituto Neurologico "Carlo Besta"
14 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
15 2I - Infection et inflammation
16 HUG - Hôpitaux Universitaires de Genève
17 University of Texas
18 IRCCS Ist Tumori Giovanni Paolo II, Bari, Italy
19 Fdn IRCCS Ist Neurol Carlo Besta, IFOM IEO Campus, Milan, Italy
20 EPFL - Ecole Polytechnique Fédérale de Lausanne
Patrizia Andreozzi
- Fonction : co premier-auteur
Marie Galloux
- Fonction : Auteur
- PersonId : 764302
- ORCID : 0000-0001-7477-8489
- IdRef : 104918055
Ronan Le Goffic
- Fonction : Auteur
- PersonId : 747849
- IdHAL : ronan-le-goffic
- ORCID : 0000-0002-2012-0064
- IdRef : 061595888
Jean Francois Eleouet
- Fonction : Auteur
- PersonId : 1151144
- IdHAL : jean-francois-eleouet
- ORCID : 0000-0002-7361-4885
- IdRef : 128009861
Laurent Kaiser
- Fonction : Auteur
- PersonId : 756519
- IdRef : 083946241
David Lembo
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 981144
Connectez-vous pour contacter l'auteur
Résumé
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 (similar to 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.