期刊
MOLECULES
卷 26, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/molecules26092593
关键词
antiviral; drug repurposing; SARS-CoV-2; influenza; structure-based drug design; inflammation; nucleoprotein; oligomerization
资金
- Sorbonne University
- Foundation of Sorbonne University
- INSERM REACTing (REsearch & ACtion emergING infectious diseases)
- CNRS
- Merieux research grant (TO)
- Merieux research grant (MRC)
- Merieux research grant (VirPath team)
- Assistance Publique-Hopitaux de Paris APHP
The study investigates the efficacy of naproxen as an antiviral drug against SARS-CoV-2, finding that it can inhibit viral replication in infected cells and protect respiratory epithelium from damage. Compared to other tested drugs, naproxen combines antiviral and anti-inflammatory properties.
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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