Molecules (Apr 2021)

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

  • 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

DOI
https://doi.org/10.3390/molecules26092593
Journal volume & issue
Vol. 26, no. 9
p. 2593

Abstract

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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.

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