CFTR Inhibitors Display In Vitro Antiviral Activity against SARS-CoV-2

  • Cells. 2023 Feb 28;12(5):776. doi: 10.3390/cells12050776.
Anna Lagni  1 ,  Virginia Lotti  1 ,  Erica Diani  1 ,  Giada Rossini  2 ,  Ercole Concia  3 ,  Claudio Sorio  4 ,  Davide Gibellini  1
Affiliations
  • 1. Microbiology Section, Department of Diagnostic and Public Health, University of Verona, 37134 Verona, Italy.
  • 2. Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
  • 3. Department of Diagnostic and Public Health, University of Verona, 37134 Verona, Italy.
  • 4. General Pathology Section, Department of Medicine, University of Verona, 37134 Verona, Italy.
PMID: 36899912 DOI: 10.3390/cells12050776
Abstract

Several reports have indicated that SARS-CoV-2 Infection displays unexpected mild clinical manifestations in people with cystic fibrosis (pwCF), suggesting that CFTR expression and function may be involved in the SARS-CoV-2 life cycle. To evaluate the possible association of CFTR activity with SARS-CoV-2 replication, we tested the Antiviral activity of two well-known CFTR inhibitors (IOWH-032 and PPQ-102) in wild type (WT)-CFTR bronchial cells. SARS-CoV-2 replication was inhibited by IOWH-032 treatment, with an IC50 of 4.52 μM, and by PPQ-102, with an IC50 of 15.92 μM. We confirmed this Antiviral effect on primary cells (MucilAirTM wt-CFTR) using 10 μM IOWH-032. According to our results, CFTR inhibition can effectively tackle SARS-CoV-2 Infection, suggesting that CFTR expression and function might play an important role in SARS-CoV-2 replication, revealing new perspectives on the mechanisms governing SARS-CoV-2 Infection in both normal and CF individuals, as well as leading to potential novel treatments.

Keywords
CFTR; CFTR inhibitors; IOWH-032; PPQ-102; SARS-CoV-2; antiviral; cystic fibrosis.
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