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The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells

Leach, DA and Mohr, A and Giotis, ES and Cil, E and Isac, AM and Yates, LL and Barclay, WS and Zwacka, RM and Bevan, CL and Brooke, GN (2021) 'The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells.' Nature Communications, 12 (1). 4068-. ISSN 2041-1723

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SARS-CoV-2 attacks various organs, most destructively the lung, and cellular entry requires two host cell surface proteins: ACE2 and TMPRSS2. Downregulation of one or both of these is thus a potential therapeutic approach for COVID-19. TMPRSS2 is a known target of the androgen receptor, a ligand-activated transcription factor; androgen receptor activation increases TMPRSS2 levels in various tissues, most notably prostate. We show here that treatment with the antiandrogen enzalutamide—a well-tolerated drug widely used in advanced prostate cancer—reduces TMPRSS2 levels in human lung cells and in mouse lung. Importantly, antiandrogens significantly reduced SARS-CoV-2 entry and infection in lung cells. In support of this experimental data, analysis of existing datasets shows striking co-expression of AR and TMPRSS2, including in specific lung cell types targeted by SARS-CoV-2. Together, the data presented provides strong evidence to support clinical trials to assess the efficacy of antiandrogens as a treatment option for COVID-19.

Item Type: Article
Uncontrolled Keywords: Lung; Animals; Humans; Mice; Benzamides; Nitriles; Phenylthiohydantoin; Androgen Antagonists; Serine Endopeptidases; Down-Regulation; Female; Male; Virus Internalization; COVID-19; Angiotensin-Converting Enzyme 2; SARS-CoV-2
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 05 Jul 2021 07:00
Last Modified: 02 Feb 2022 12:48

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