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

Author

Listed:
  • D. A. Leach

    (Imperial College London)

  • A. Mohr

    (University of Essex)

  • E. S. Giotis

    (University of Essex
    Imperial College London)

  • E. Cil

    (University of Essex)

  • A. M. Isac

    (University of Essex)

  • L. L. Yates

    (Imperial College London)

  • W. S. Barclay

    (Imperial College London)

  • R. M. Zwacka

    (University of Essex)

  • C. L. Bevan

    (Imperial College London)

  • G. N. Brooke

    (Imperial College London
    University of Essex)

Abstract

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.

Suggested Citation

  • D. A. Leach & A. Mohr & E. S. Giotis & E. Cil & A. M. Isac & L. L. Yates & W. S. Barclay & R. M. Zwacka & C. L. Bevan & G. N. Brooke, 2021. "The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24342-y
    DOI: 10.1038/s41467-021-24342-y
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