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Macromolecular Viral Entry Inhibitors as Broad-Spectrum First-Line Antivirals with Activity against SARS-CoV-2

Authors :
Rüdiger Groß
Lívia Mesquita Dias Loiola
Leila Issmail
Nadja Uhlig
Valentina Eberlein
Carina Conzelmann
Lia‐Raluca Olari
Lena Rauch
Jan Lawrenz
Tatjana Weil
Janis A. Müller
Mateus Borba Cardoso
Andrea Gilg
Olivia Larsson
Urban Höglund
Sandra Axberg Pålsson
Anna Selch Tvilum
Kaja Borup Løvschall
Maria M. Kristensen
Anna‐Lena Spetz
Fortune Hontonnou
Marie Galloux
Thomas Grunwald
Alexander N. Zelikin
Jan Münch
Virologie et Immunologie Moléculaires (VIM (UR 0892))
Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
European Commission, EC: 101003555 – Fight‐nCoV
European Research Council, ERC
Deutsche Forschungsgemeinschaft, DFG: CRC1279, KL 2544/8‐1
Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP: 2015/25406‐5, 2019/17028‐1
A.L.S., J.M., and A.N.Z. acknowledge funding by the European Research Council (EU project 101003555 – Fight‐nCoV). J.M. additionally acknowledges funding by the German Research Foundation (DFG) through 'Fokus‐Förderung COVID‐19' (FR 2974/3‐1, KL 2544/8‐1) and the CRC1279, and the Sonderfördermassnahme COVID‐19 of the MWK Baden‐Württemberg, Germany. L.M.D.L. and M.B.C. thank the São Paulo Research Foundation ‐ FAPESP (process numbers: 2015/25406‐5 and 2019/17028‐1). The authors are grateful to Jean‐François Eléouët (INRAE Jouy‐en‐Josas, France) and Marie‐Anne Rameix‐Welti (UVSQ, St Quentin‐en Yvelines, France) for providing rHRSV Luc virus. The authors thank Infectiology of fishes and rodent facility (IERP, INRAE, doi: 10.15454/1.5572427140471238E12) to animals’ facilities, and the Emerg'in platform for access to IVIS200 that was financed by the Region Ile De France (SESAME), Maria Valsjö for her practical expertise in toxicology experiments, as well as Isabelle Ryman and Maria Erlandsson for histopathological analysis. The authors also kindly thank Isabell Schulz and Anne‐Kathrin Donner for excellent technical assistance, Jasmin Fertey for providing high titer virus stocks of SARS‐CoV‐2, and Alexandra Rockstroh for the optimized SARS‐CoV‐2 detection protocol.
A.L.S., J.M., and A.N.Z. acknowledge funding by the European Research Council (EU project 101003555 – Fight-nCoV). J.M. additionally acknowledges funding by the German Research Foundation (DFG) through 'Fokus-Förderung COVID-19' (FR 2974/3-1, KL 2544/8-1) and the CRC1279, and the Sonderfördermassnahme COVID-19 of the MWK Baden-Württemberg, Germany. L.M.D.L. and M.B.C. thank the São Paulo Research Foundation - FAPESP (process numbers: 2015/25406-5 and 2019/17028-1). The authors are grateful to Jean-François Eléouët (INRAE Jouy-en-Josas, France) and Marie-Anne Rameix-Welti (UVSQ, St Quentin-en Yvelines, France) for providing rHRSV Luc virus. The authors thank Infectiology of fishes and rodent facility (IERP, INRAE, doi: 10.15454/1.5572427140471238E12) to animals’ facilities, and the Emerg'in platform for access to IVIS200 that was financed by the Region Ile De France (SESAME), Maria Valsjö for her practical expertise in toxicology experiments, as well as Isabelle Ryman and Maria Erlandsson for histopathological analysis. The authors also kindly thank Isabell Schulz and Anne-Kathrin Donner for excellent technical assistance, Jasmin Fertey for providing high titer virus stocks of SARS-CoV-2, and Alexandra Rockstroh for the optimized SARS-CoV-2 detection protocol. Open Access funding enabled and organized by Projekt DEAL.
European Project: 101003555,H2020, RIA,H2020-SC1-PHE-CORONAVIRUS-2020,Fight-nCoV(2020)
Publica
Source :
Advanced Science, Advanced Science, 2022, 9 (20), pp.2201378. ⟨10.1002/advs.202201378⟩, Groß, R, Dias Loiola, L M, Issmail, L, Uhlig, N, Eberlein, V, Conzelmann, C, Olari, L R, Rauch, L, Lawrenz, J, Weil, T, Müller, J A, Cardoso, M B, Gilg, A, Larsson, O, Höglund, U, Pålsson, S A, Tvilum, A S, Løvschall, K B, Kristensen, M M, Spetz, A L, Hontonnou, F, Galloux, M, Grunwald, T, Zelikin, A N & Münch, J 2022, ' Macromolecular Viral Entry Inhibitors as Broad-Spectrum First-Line Antivirals with Activity against SARS-CoV-2 ', Advanced Science, vol. 9, no. 20, 2201378 . https://doi.org/10.1002/advs.202201378, Adv. Sci.
Publication Year :
2022
Publisher :
HAL CCSD, 2022.

Abstract

International audience; Inhibitors of viral cell entry based on poly(styrene sulfonate) and its core–shell nanoformulations based on gold nanoparticles are investigated against a panel of viruses, including clinical isolates of SARS-CoV-2. Macromolecular inhibitors are shown to exhibit the highly sought-after broad-spectrum antiviral activity, which covers most analyzed enveloped viruses and all of the variants of concern for SARS-CoV-2 tested. The inhibitory activity is quantified in vitro in appropriate cell culture models and for respiratory viral pathogens (respiratory syncytial virus and SARS-CoV-2) in mice. Results of this study comprise a significant step along the translational path of macromolecular inhibitors of virus cell entry, specifically against enveloped respiratory viruses.

Details

Language :
English
ISSN :
21983844
Database :
OpenAIRE
Journal :
Advanced Science, Advanced Science, 2022, 9 (20), pp.2201378. ⟨10.1002/advs.202201378⟩, Groß, R, Dias Loiola, L M, Issmail, L, Uhlig, N, Eberlein, V, Conzelmann, C, Olari, L R, Rauch, L, Lawrenz, J, Weil, T, Müller, J A, Cardoso, M B, Gilg, A, Larsson, O, Höglund, U, Pålsson, S A, Tvilum, A S, Løvschall, K B, Kristensen, M M, Spetz, A L, Hontonnou, F, Galloux, M, Grunwald, T, Zelikin, A N & Münch, J 2022, ' Macromolecular Viral Entry Inhibitors as Broad-Spectrum First-Line Antivirals with Activity against SARS-CoV-2 ', Advanced Science, vol. 9, no. 20, 2201378 . https://doi.org/10.1002/advs.202201378, Adv. Sci.
Accession number :
edsair.doi.dedup.....d7dde02e5df70842522aebdc21f15581
Full Text :
https://doi.org/10.1002/advs.202201378⟩