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.
- MeSH
- antiflogistika nesteroidní farmakologie MeSH
- antivirové látky farmakologie MeSH
- buněčné linie MeSH
- Cercopithecus aethiops MeSH
- COVID-19 MeSH
- farmakoterapie COVID-19 MeSH
- lidé MeSH
- naproxen farmakologie MeSH
- nukleoproteiny antagonisté a inhibitory metabolismus MeSH
- přehodnocení terapeutických indikací léčivého přípravku MeSH
- replikace viru účinky léků MeSH
- SARS-CoV-2 účinky léků fyziologie MeSH
- simulace molekulového dockingu MeSH
- Vero buňky MeSH
- virové proteiny antagonisté a inhibitory metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH