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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-04, Vol.26 (9), p.2593
• Main Authors: Terrier, Olivier, Dilly, Sébastien, Pizzorno, Andrés, Chalupska, Dominika, Humpolickova, Jana, Bouřa, Evžen, Berenbaum, Francis, Quideau, Stéphane, Lina, Bruno, Fève, Bruno, Adnet, Frédéric, Sabbah, Michèle, Rosa-Calatrava, Manuel, Maréchal, Vincent, Henri, Julien, Slama-Schwok, Anny
• Format: Article
• Language: English
• Subjects: Animals; Anisotropy; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; antiviral; Antiviral activity; Antiviral Agents - pharmacology; Celecoxib; Cell Line; Chlorocebus aethiops; Coronaviruses; COVID-19; COVID-19 - drug therapy; COX-2 inhibitors; Cyclooxygenase-2; Drug Repositioning; drug repurposing; Epithelium; Fluorescence; Fluorescence spectroscopy; Humans; Inflammation; influenza; Influenza A; Life Sciences; Light scattering; Middle East respiratory syndrome; Molecular Docking Simulation; Molecular modelling; Naproxen; Naproxen - pharmacology; Nonsteroidal anti-inflammatory drugs; Nucleoproteins - antagonists & inhibitors; Nucleoproteins - metabolism; Oligomerization; Paracetamol; Photon correlation spectroscopy; Public health; Replication; Respiratory tract; SARS-CoV-2; SARS-CoV-2 - drug effects; SARS-CoV-2 - physiology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; structure-based drug design; Vero Cells; Viral Proteins - antagonists & inhibitors; Viral Proteins - metabolism; Virus Replication - drug effects; Viruses
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26092593

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.