tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], S?bastien Dilly[SUP] 2 [/SUP], Andr?s Pizzorno[SUP] 1 [/SUP], Dominika Chalupska[SUP] 3 [/SUP], Jana Humpolickova[SUP] 3 [/SUP], Ev?en Bou?a[SUP] 3 [/SUP], Francis Berenbaum[SUP] 4 [/SUP], St?phane Quideau[SUP] 5 6 [/SUP], Bruno Lina[SUP] 1 [/SUP], Bruno F?ve[SUP] 7 8 [/SUP], Fr?d?ric Adnet[SUP] 9 [/SUP], Mich?le Sabbah[SUP] 2 [/SUP], Manuel Rosa-Calatrava[SUP] 1 [/SUP], Vincent Mar?chal[SUP] 2 [/SUP], Julien Henri[SUP] 10 [/SUP], Anny Slama-Schwok[SUP] 2 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], S?bastien Dilly[SUP] 2 [/SUP], Andr?s Pizzorno[SUP] 1 [/SUP], Dominika Chalupska[SUP] 3 [/SUP], Jana Humpolickova[SUP] 3 [/SUP], Ev?en Bou?a[SUP] 3 [/SUP], Francis Berenbaum[SUP] 4 [/SUP], St?phane Quideau[SUP] 5 6 [/SUP], Bruno Lina[SUP] 1 [/SUP], Bruno F?ve[SUP] 7 8 [/SUP], Fr?d?ric Adnet[SUP] 9 [/SUP], Mich?le Sabbah[SUP] 2 [/SUP], Manuel Rosa-Calatrava[SUP] 1 [/SUP], Vincent Mar?chal[SUP] 2 [/SUP], Julien Henri[SUP] 10 [/SUP], Anny Slama-Schwok[SUP] 2 [/SUP]
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.