Apalutamide Prevents SARS-CoV-2 Infection in Lung Epithelial Cells and in Human Nasal Epithelial Cells - Université Paris-Est-Créteil-Val-de-Marne Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2023

Apalutamide Prevents SARS-CoV-2 Infection in Lung Epithelial Cells and in Human Nasal Epithelial Cells

Margot Morin-Dewaele
  • Function : Author
Francois Berry
  • Function : Author
Julien Fouchet
  • Function : Author
Sophie Bartier
  • Function : Author
Anais Dufros Duval
  • Function : Author
Eric Huet
  • Function : Author
  • PersonId : 1213934
  • IdHAL : eric-huet
Bruno Louis
  • Function : Author
André Coste
  • Function : Author
Émilie Béquignon
Philippe Le Corvoisier
  • Function : Author
Jean-Michel Pawlotsky
  • Function : Author
Alexandre de la Taille
  • Function : Author
Patrice Bruscella

Abstract

In early 2020, the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, and rapidly propagated worldwide causing a global health emergency. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) protein for cell entry, followed by proteolytic cleavage of the Spike (S) protein by the transmembrane serine protease 2 (TMPRSS2), allowing fusion of the viral and cellular membranes. Interestingly, TMPRSS2 is a key regulator in prostate cancer (PCa) progression which is regulated by androgen receptor (AR) signaling. Our hypothesis is that the AR signaling may regulate the expression of TMPRSS2 in human respiratory cells and thus influence the membrane fusion entry pathway of SARS-CoV-2. We show here that TMPRSS2 and AR are expressed in Calu-3 lung cells. In this cell line, TMPRSS2 expression is regulated by androgens. Finally, pre-treatment with anti-androgen drugs such as apalutamide significantly reduced SARS-CoV-2 entry and infection in Calu-3 lung cells but also in primary human nasal epithelial cells. Altogether, these data provide strong evidence to support the use of apalutamide as a treatment option for the PCa population vulnerable to severe COVID-19.
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Dates and versions

hal-03978879 , version 1 (08-02-2023)

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Amene Majidipur, Margot Morin-Dewaele, Jeanne Gaspar Lopes, Francois Berry, Julien Fouchet, et al.. Apalutamide Prevents SARS-CoV-2 Infection in Lung Epithelial Cells and in Human Nasal Epithelial Cells. International Journal of Molecular Sciences, 2023, 24 (4), pp.3288. ⟨10.3390/ijms24043288⟩. ⟨hal-03978879⟩

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