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

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Molecules


. 2021 Apr 29;26(9):2593.
doi: 10.3390/molecules26092593.
Antiviral Properties of the NSAID Drug Naproxen Targeting the Nucleoprotein of SARS-CoV-2 Coronavirus


Olivier Terrier ¹ , S?bastien Dilly ² , Andr?s Pizzorno ¹ , Dominika Chalupska ³ , Jana Humpolickova ³ , Ev?en Bou?a ³ , Francis Berenbaum ⁴ , St?phane Quideau ^{5 6} , Bruno Lina ¹ , Bruno F?ve ^{7 8} , Fr?d?ric Adnet ⁹ , Mich?le Sabbah ² , Manuel Rosa-Calatrava ¹ , Vincent Mar?chal ² , Julien Henri ¹⁰ , Anny Slama-Schwok ²



Affiliations

• PMID: 33946802
• DOI: 10.3390/molecules26092593

Abstract

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.

Keywords: SARS-CoV-2; antiviral; drug repurposing; inflammation; influenza; nucleoprotein; oligomerization; structure-based drug design.