Apalutamide Prevents SARS-CoV-2 Infection in Lung Epithelial Cells and in Human Nasal Epithelial Cells
Amene Majidipur, Margot Morin-Dewaele, Jeanne Gaspar Lopes, Francois Berry, Julien Fouchet, Sophie Bartier, Anais Dufros Duval, Pascale Soyeux, Eric Huet, Bruno Louis, André Coste, Émilie Béquignon, Carolina Saldana, Philippe Le Corvoisier, Damien Destouches, Jean-Michel Pawlotsky, Alexandre De La Taille, Francis Vacherot, Patrice Bruscella, Virginie Firlej
International Journal of Molecular Sciences, doi:10.3390/ijms24043288
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.
Supplementary Materials: The following supporting information can be downloaded at https:// www.mdpi.com/article/10.3390/ijms24043288/s1, Figure S1 : Effect of AR antagonists on TMPRSS2 expression in lung and prostate cells,
Conflicts of Interest: The sponsors had no role in the design, execution, interpretation, or writing of the study.
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'abstract': '<jats:p>In early 2020, the novel pathogenic severe acute respiratory syndrome coronavirus 2 '
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'health emergency. SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) protein for '
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'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.</jats:p>',
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