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

• Main Authors: Olivier Terrier, 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, Anny Slama-Schwok
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Molecules
• Subjects: antiviral; drug repurposing; SARS-CoV-2; influenza; structure-based drug design; inflammation
• Online Access: https://www.mdpi.com/1420-3049/26/9/2593

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.