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Article

Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus

1
CIRI, Centre International de Recherche en Infectiologie, (Team VirPath), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, F-69007 Lyon, France
2
Cancer Biology and Therapeutics Team, INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Sorbonne Universitè, F-75012 Paris, France
3
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, 11720 Prague, Czech Republic
4
INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Sorbonne University, and Department of Rheumatology, AP-HP Saint-Antoine Hospital, F-75012 Paris, France
5
ISM, UMR-CNRS 5255, Université de Bordeaux, F-33405 Talence, France
6
Institut Universitaire de France, F-75231 Paris, France
7
Genetic and acquired lipodystrophies Team, INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Sorbonne Université, F-75012 Paris, France
8
Department of Endocrinology, AP-HP Saint-Antoine Hospital, Institut Hospitalo-Universitaire de Cardio-métabolisme et Nutrition (ICAN), CRMR PRISIS, F-75012 Paris, France
9
Service d’Urgences–SAMU–SMUR, Hôpital Avicenne, AP-HP, F-93000 Bobigny, France
10
Laboratoire de Biologie Computationnelle et Quantitative, Institut de Biologie Paris-Seine, UMR-CNRS 7238, Sorbonne Université, F-75005 Paris, France
*
Author to whom correspondence should be addressed.
The second authors contributed equally.
M.R.-C. and V.M. contributed equally.
Academic Editor: Luděk Eyer
Molecules 2021, 26(9), 2593; https://doi.org/10.3390/molecules26092593
Received: 5 April 2021 / Revised: 22 April 2021 / Accepted: 26 April 2021 / Published: 29 April 2021
(This article belongs to the Special Issue Recent Advances in Antiviral Agents)
There is an urgent need for specific antiviral treatments directed against SARS-CoV-2 to prevent the most severe forms of COVID-19. By drug repurposing, affordable therapeutics could be supplied worldwide in the present pandemic context. Targeting the nucleoprotein N of the SARS-CoV-2 coronavirus could be a strategy to impede viral replication and possibly other essential functions associated with viral N. The antiviral properties of naproxen, a non-steroidal anti-inflammatory drug (NSAID) that was previously demonstrated to be active against Influenza A virus, were evaluated against SARS-CoV-2. Intrinsic fluorescence spectroscopy, fluorescence anisotropy, and dynamic light scattering assays demonstrated naproxen binding to the nucleoprotein of SARS-Cov-2 as predicted by molecular modeling. Naproxen impeded recombinant N oligomerization and inhibited viral replication in infected cells. In VeroE6 cells and reconstituted human primary respiratory epithelium models of SARS-CoV-2 infection, naproxen specifically inhibited viral replication and protected the bronchial epithelia against SARS-CoV-2-induced damage. No inhibition of viral replication was observed with paracetamol or the COX-2 inhibitor celecoxib. Thus, among the NSAID tested, only naproxen combined antiviral and anti-inflammatory properties. Naproxen addition to the standard of care could be beneficial in a clinical setting, as tested in an ongoing clinical study. View Full-Text
Keywords: antiviral; drug repurposing; SARS-CoV-2; influenza; structure-based drug design; inflammation; nucleoprotein; oligomerization antiviral; drug repurposing; SARS-CoV-2; influenza; structure-based drug design; inflammation; nucleoprotein; oligomerization
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MDPI and ACS Style

Terrier, O.; Dilly, S.; Pizzorno, A.; Chalupska, D.; Humpolickova, J.; Bouřa, E.; Berenbaum, F.; Quideau, S.; Lina, B.; Fève, B.; Adnet, F.; Sabbah, M.; Rosa-Calatrava, M.; Maréchal, V.; Henri, J.; Slama-Schwok, A. Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus. Molecules 2021, 26, 2593. https://doi.org/10.3390/molecules26092593

AMA Style

Terrier O, Dilly S, Pizzorno A, Chalupska D, Humpolickova J, Bouřa E, Berenbaum F, Quideau S, Lina B, Fève B, Adnet F, Sabbah M, Rosa-Calatrava M, Maréchal V, Henri J, Slama-Schwok A. Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus. Molecules. 2021; 26(9):2593. https://doi.org/10.3390/molecules26092593

Chicago/Turabian Style

Terrier, Olivier, Sébastien Dilly, Andrés Pizzorno, Dominika Chalupska, Jana Humpolickova, Evžen Bouřa, Francis Berenbaum, Stéphane Quideau, Bruno Lina, Bruno Fève, Frédéric Adnet, Michèle Sabbah, Manuel Rosa-Calatrava, Vincent Maréchal, Julien Henri, and Anny Slama-Schwok. 2021. "Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus" Molecules 26, no. 9: 2593. https://doi.org/10.3390/molecules26092593

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