Analgesics
Antiandrogens
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Abstract
All antiandrogen studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19early.org COVID-19 treatment researchAntiandrogenAntiandrogens (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

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

Leach et al., Nature Communications, doi:10.1038/s41467-021-24342-y
Jul 2021  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
5th treatment shown to reduce risk in August 2020
 
*, now known with p = 0.000000043 from 50 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments. c19early.org
In Vitro and animal study showing that the antiandrogen enzalutamide reduces TMPRSS2 levels in human lung cells and in mouse lungs.
3 preclinical studies support the efficacy of antiandrogens for COVID-19:
Leach et al., 1 Jul 2021, peer-reviewed, 10 authors.
This PaperAntiandrogensAll
The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells
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
Nature Communications, doi:10.1038/s41467-021-24342-y
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 coexpression 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.
Author contributions Competing interests The authors declare no competing interests. Additional information Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41467-021-24342-y. Correspondence and requests for materials should be addressed to C.L.B. or G.N.B. Peer review information Nature Communications thanks Changmeng Cai and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available. Reprints and permission information is available at http://www.nature.com/reprints Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
Asselta, Paraboschi, Mantovani, Duga, ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy, Aging
Baratchian, Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes, Sci. Rep
Blanco-Melo, Imbalanced host response to SARS-CoV-2 drives development of COVID-19, Cell
Brooke, Antiandrogens act as selective androgen receptor modulators at the proteome level in prostate cancer cells, Mol. Cell. Proteom
Brooke, Bevan, The role of androgen receptor mutations in prostate cancer progression, Curr. Genomics
Brooke, Engineered repressors are potent inhibitors of androgen receptor activity, Oncotarget
Brooke, FUS/TLS is a novel mediator of androgen-dependent cellcycle progression and prostate cancer growth, Cancer Res
Brooke, Prischi, Structural and functional modelling of SARS-CoV-2 entry in animal models, Sci. Rep
Cano, The co-chaperone p23 promotes prostate cancer motility and metastasis, Mol. Oncol
Chen, Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, Lancet
Clinckemalie, Androgen regulation of the TMPRSS2 gene and the effect of a SNP in an androgen response element, Mol. Endocrinol
Consortium, An integrated encyclopedia of DNA elements in the human genome, Nature
Consortium, Genetic effects on gene expression across human tissues, Nature
Crawford, Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations, Prostate Cancer Prostatic Dis
Dart, Novel trifluoromethylated enobosarm analogues with potent antiandrogenic activity in vitro and tissue selectivity in vivo, Mol. Cancer Ther
Dart, Waxman, Aboagye, Bevan, Visualising androgen receptor activity in male and female mice, PLoS One
Deng, Rasool, Russell, Natesan, Asangani, Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19, iScience
Fornes, update of the open-access database of transcription factor binding profiles, Nucleic Acids Res
Gamazon, Using an atlas of gene regulation across 44 human tissues to inform complex disease-and trait-associated variation, Nat. Genet
Gertz, Distinct properties of cell-type-specific and shared transcription factor binding sites, Mol. Cell
Giotis, Entry of the bat influenza H17N10 virus into mammalian cells is enabled by the MHC class II HLA-DR receptor, Nat. Microbiol
Glont, Chernukhin, Carroll, Comprehensive genomic analysis reveals that the pioneering function of FOXA1 is independent of hormonal signaling, Cell Rep
Glowacka, Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response, J. Virol
Goren, A preliminary observation: male pattern hair loss among hospitalized COVID-19 patients in Spain -a potential clue to the role of androgens in COVID-19 severity, J. Cosmet. Dermatol
Grant, Androgen receptor and Ki67 expression and survival outcomes in non-small cell lung cancer, Horm. Cancer
Grant, Bailey, Noble, FIMO: scanning for occurrences of a given motif, Bioinformatics
Hay, Negative regulation of the androgen receptor gene through a primate-specific androgen response element present in the 5' UTR, Horm. Cancer
Hoffmann, Kleine-Weber, Pohlmann, A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells, Mol. Cell
Hoffmann, SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell
Ibrahim, Abdelmalek, Elshahat, Elfiky, COVID-19 spike-host cell receptor GRP78 binding site prediction, J. Infect
Iwata-Yoshikawa, TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection, J Virol
Jeong, Research resource: diagnostic and therapeutic potential of nuclear receptor expression in lung cancer, Mol. Endocrinol
Jia, Pulmonary angiotensin-converting enzyme 2 (ACE2) and inflammatory lung disease, Shock
Jin, Gender differences in patients with COVID-19: focus on severity and mortality, Front Public Health
Kim, Heinlein, Hackman, Nelson, Phenotypic analysis of mice lacking the Tmprss2-encoded protease, Mol. Cell Biol
Ksiazek, A novel coronavirus associated with severe acute respiratory syndrome, N. Engl. J. Med
Kuba, A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury, Nat. Med
Kärber, Beitrag zur kollektiven Behandlung pharmakologischer Reihenversuche. Naunyn-Schmiedebergs Arch, f.ür. experimentelle Pathologie und Pharmakologie
Leach, Cell-lineage specificity and role of AP-1 in the prostate fibroblast androgen receptor cistrome, Mol. Cell. Endocrinol
Li, Distinct mechanisms for TMPRSS2 expression explain organspecific inhibition of SARS-CoV-2 infection by enzalutamide, Nat. Commun
Lin, Chang, Ko, Liao, Lo, Reduction of androgen receptor expression by benzo[alpha]pyrene and 7,8-dihydro-9,10-epoxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene in human lung cells, Biochem Pharm
Lin, Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2, Cancer Res
Long, Wright, Molesti, Temperton, Barclay, Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry, F1000Res
Lukassen, SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells, EMBO J
Mangelsdorf, The nuclear receptor superfamily: the second decade, Cell
Matsuyama, Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2, J. Virol
Mccoy, Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19?, J. Cosmet. Dermatol
Mckay, Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice, Nat. Commun
Mikkonen, Pihlajamaa, Sahu, Zhang, Janne, Androgen receptor and androgen-dependent gene expression in lung, Mol. Cell Endocrinol
Mina, Yoder, Sharma, Targeting the androgen receptor in triplenegative breast cancer: current perspectives, Onco Targets Ther
Montopoli, Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (n=4532), Ann. Oncol
Need, The unique transcriptional response produced by concurrent estrogen and progesterone treatment in breast cancer cells results in upregulation of growth factor pathways and switching from a Luminal A to a Basal-like subtype, BMC Cancer
Nuhn, Update on systemic prostate cancer therapies: management of metastatic castration-resistant prostate cancer in the era of precision oncology, Eur. Urol
Peacock, The furin cleavage site of SARS-CoV-2 spike protein is a key determinant for transmission due to enhanced replication in airway cells, doi:10.1101/2020.09.30.318311
Periyasamy, APOBEC3B-mediated cytidine deamination is required for estrogen receptor action in breast cancer, Cell Rep
Pihlajamaa, The phytoestrogen genistein is a tissue-specific androgen receptor modulator, Endocrinology
Piva, Sabanovic, Cecati, Giulietti, Expression and co-expression analyses of TMPRSS2, a key element in COVID-19, Eur. J. Clin. Microbiol. Infect. Dis
Qiao, Targeting transcriptional regulation of SARS-CoV-2 entry factors ACE2 and TMPRSS2, Proc. Natl Acad. Sci
Reyfman, Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis, Am. J. Respir. Crit. Care Med
Rice, Malhotra, Stoyanova, Second-generation antiandrogens: from discovery to standard of care in castration resistant prostate cancer, Front Oncol
Rockx, Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model, Science
Sahu, FoxA1 specifies unique androgen and glucocorticoid receptor binding events in prostate cancer cells, Cancer Res
Samuel, Androgen signaling regulates SARS-CoV-2 receptor levels and is associated with severe COVID-19 symptoms in men, Cell Stem Cell
Severson, Characterizing steroid hormone receptor chromatin binding landscapes in male and female breast cancer, Nat. Commun
Shang, Cell entry mechanisms of SARS-CoV-2, Proc. Natl Acad. Sci
Shulla, A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry, J. Virol
Stelloo, Endogenous androgen receptor proteomic profiling reveals genomic subcomplex involved in prostate tumorigenesis, Oncogene
Stopsack, Mucci, Antonarakis, Nelson, Kantoff, TMPRSS2 and COVID-19: serendipity or opportunity for intervention?, Cancer Disco
Student, Hejmo, Poterala-Hejmo, Lesniak, Buldak, Antiandrogen hormonal therapy for cancer and other diseases, Eur. J. Pharm
Taberlay, Three-dimensional disorganization of the cancer genome occurs coincident with long-range genetic and epigenetic alterations, Genome Res
Torjesen, Sandnes, Serum testosterone in women as measured by an automated immunoassay and a RIA, Clin. Chem
Ustuner, Cause of androgenic alopecia: crux of the matter, Plast. Reconstr. Surg. Glob. Open
Wambier, Androgenetic alopecia present in the majority of hospitalized COVID-19 patients -the "Gabrin sign, J. Am. Acad. Dermatol
Wang, TMPRSS2 transcriptional inhibition as a therapeutic strategy for COVID-19, Preprint
Wilson, Mcphaul, A and B forms of the androgen receptor are expressed in a variety of human tissues, Mol. Cell Endocrinol
Yoon, Kim, Choi, Won, Lim, Direct activation of TGF-beta1 transcription by androgen and androgen receptor complex in Huh7 human hepatoma cells and its tumor in nude mice, J. Cell Biochem
Yuki, Fujiogi, Koutsogiannaki, COVID-19 pathophysiology: a review, Clin. Immunol
Zang, TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes, Sci. Immunol
Zarnegar, Reinitz, Newman, Clarke, Targeted chromatin ligation, a robust epigenetic profiling technique for small cell numbers, Nucleic Acids Res
Zhang, Risk factors for disease severity, unimprovement, and mortality in COVID-19 patients in Wuhan, China, Clin. Microbiol. Infect
Zhou, A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature
Loading..
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop   
Submit