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

{ 'indexed': { 'date-parts': [[2023, 12, 30]], 'date-time': '2023-12-30T08:01:40Z', 'timestamp': 1703923300816}, 'reference-count': 81, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2021, 7, 1]], 'date-time': '2021-07-01T00:00:00Z', 'timestamp': 1625097600000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2021, 7, 1]], 'date-time': '2021-07-01T00:00:00Z', 'timestamp': 1625097600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>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.</jats:p>', 'DOI': '10.1038/s41467-021-24342-y', 'type': 'journal-article', 'created': {'date-parts': [[2021, 7, 1]], 'date-time': '2021-07-01T10:05:24Z', 'timestamp': 1625133924000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 48, 'title': 'The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in ' 'human lung cells', 'prefix': '10.1038', 'volume': '12', 'author': [ {'given': 'D. A.', 'family': 'Leach', 'sequence': 'first', 'affiliation': []}, {'given': 'A.', 'family': 'Mohr', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-8908-7824', 'authenticated-orcid': False, 'given': 'E. S.', 'family': 'Giotis', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-5097-1548', 'authenticated-orcid': False, 'given': 'E.', 'family': 'Cil', 'sequence': 'additional', 'affiliation': []}, {'given': 'A. M.', 'family': 'Isac', 'sequence': 'additional', 'affiliation': []}, {'given': 'L. L.', 'family': 'Yates', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-3948-0895', 'authenticated-orcid': False, 'given': 'W. S.', 'family': 'Barclay', 'sequence': 'additional', 'affiliation': []}, {'given': 'R. M.', 'family': 'Zwacka', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-7533-0552', 'authenticated-orcid': False, 'given': 'C. L.', 'family': 'Bevan', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-4501-4134', 'authenticated-orcid': False, 'given': 'G. 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