Journal
ISCIENCE
Volume 25, Issue 10, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2022.105066
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Funding
- French National Research Agency [ANR-10-INBS-04]
- Region Ile-de France (program DIM1Health)
- Institut Pasteur
- CNRS
- Montpellier University through a Montpellier Universite d'Excellence (MUSE)
- French Agency for Research through the Fondation de la Recherche Medicale (ANR COVID19)
- Canceropole Ile-de-France
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This study highlights the potential of Auranofin in inhibiting NF-kappa B pathway to alleviate inflammation, prevent SARS-CoV-2 infection, and counteract key steps of viral entry into host cells.
Patients with severe COVID-19 show an altered immune response that fails to control the viral spread and suffer from exacerbated inflammatory response, which eventually can lead to death. A major challenge is to develop an effective treatment for COVID-19. NF-kappa B is a major player in innate immunity and inflammatory process. By a high-throughput screening approach, we identified FDA-approved compounds that inhibit the NF-kappa B pathway and thus dampen inflammation. Among these, we show that Auranofin prevents post-translational modifications of NF-kappa B effectors and their recruitment into activating complexes in response to SARS-CoV-2 infection or cytokine stimulation. In addition, we demonstrate that Auranofin counteracts several steps of SARS-CoV-2 infection. First, it inhibits a raft-dependent endocytic pathway involved in SARS-CoV-2 en-try into host cells; Second, Auranofin alters the ACE2 mobility at the plasma mem-brane. Overall, Auranofin should prevent SARS-CoV-2 infection and inflammatory damages, offering new opportunities as a repurposable drug candidate to treat COVID-19.
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