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Use of Antiandrogens as Therapeutic Agents in COVID-19 Patients

Giotis et al., Viruses, doi:10.3390/v14122728
Dec 2022  
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7th treatment shown to reduce risk in September 2020, now with p = 0.000000056 from 49 studies.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19early.org
Review of the use of antiandrogens for COVID-19. Authors discuss the gender disparity in COVID-19 outcomes, with men showing higher infection, hospitalization, and mortality rates compared to women. This difference is attributed to the role of androgens in regulating key proteins involved in SARS-CoV-2 cell entry, particularly TMPRSS2 and ACE2. Authors explore the potential of androgen receptor modulators, including androgen deprivation therapies (ADT) and antiandrogens, as treatments for COVID-19. They note that antiandrogens have shown antiviral effects against SARS-CoV-2 in vitro, but their efficacy in clinical settings remains inconclusive. The review suggests that future research should focus on combination therapies involving antiandrogens and explore next-generation antiandrogens for their potential antiviral effects. Additionally, the authors emphasize the need for a better understanding of the mechanistic roles of androgens in the respiratory tract and the exploration of TMPRSS2-independent virus entry pathways.
See Mauvais-Jarvis et al. for another review covering antiandrogen for COVID-19.
Giotis et al., 7 Dec 2022, peer-reviewed, 3 authors. Contact: e.giotis@imperial.ac.uk (corresponding author).
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Use of Antiandrogens as Therapeutic Agents in COVID-19 Patients
Efstathios S Giotis, Emine Cil, Greg N Brooke
Viruses, doi:10.3390/v14122728
, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, highlight the urgent need for more effective antivirals to combat the disease in the long run along with regularly updated vaccine boosters. One of the early risk factors identified during the COVID-19 pandemic was that men are more likely to become infected by the virus, more likely to develop severe disease and exhibit a higher likelihood of hospitalisation and mortality rates compared to women. An association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid hormones and, in particular, androgens. Several studies underlined the importance of the androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2, as well as the key role of these factors in the entry of the virus into target cells. In this context, modulating androgen signalling is a promising strategy to block viral infection, and antiandrogens could be used as a preventative measure at the pre-or early hospitalisation stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat metastatic castration-sensitive prostate cancer and other conditions, have been tested as antivirals with varying success. In this review, we summarise the most recent updates concerning the use of antiandrogens as prophylactic and therapeutic options for COVID-19.
Conflicts of Interest: The authors declare no conflict of interest.
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{ 'indexed': {'date-parts': [[2024, 7, 2]], 'date-time': '2024-07-02T13:18:22Z', 'timestamp': 1719926302487}, 'reference-count': 151, 'publisher': 'MDPI AG', 'issue': '12', 'license': [ { 'start': { 'date-parts': [[2022, 12, 7]], 'date-time': '2022-12-07T00:00:00Z', 'timestamp': 1670371200000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [{'name': 'University of Essex COVID-19 Rapid'}, {'name': 'Agile Fund'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), ' 'is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving ' 'SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well ' 'as immune and vaccine escape capabilities, highlight the urgent need for more effective ' 'antivirals to combat the disease in the long run along with regularly updated vaccine ' 'boosters. One of the early risk factors identified during the COVID-19 pandemic was that men ' 'are more likely to become infected by the virus, more likely to develop severe disease and ' 'exhibit a higher likelihood of hospitalisation and mortality rates compared to women. An ' 'association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid ' 'hormones and, in particular, androgens. Several studies underlined the importance of the ' 'androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2, as ' 'well as the key role of these factors in the entry of the virus into target cells. In this ' 'context, modulating androgen signalling is a promising strategy to block viral infection, and ' 'antiandrogens could be used as a preventative measure at the pre- or early hospitalisation ' 'stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat ' 'metastatic castration-sensitive prostate cancer and other conditions, have been tested as ' 'antivirals with varying success. In this review, we summarise the most recent updates ' 'concerning the use of antiandrogens as prophylactic and therapeutic options for ' 'COVID-19.</jats:p>', 'DOI': '10.3390/v14122728', 'type': 'journal-article', 'created': {'date-parts': [[2022, 12, 7]], 'date-time': '2022-12-07T07:49:35Z', 'timestamp': 1670399375000}, 'page': '2728', 'source': 'Crossref', 'is-referenced-by-count': 4, 'title': 'Use of Antiandrogens as Therapeutic Agents in COVID-19 Patients', 'prefix': '10.3390', 'volume': '14', 'author': [ { 'ORCID': 'http://orcid.org/0000-0001-8908-7824', 'authenticated-orcid': False, 'given': 'Efstathios S.', 'family': 'Giotis', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-5097-1548', 'authenticated-orcid': False, 'given': 'Emine', 'family': 'Cil', 'sequence': 'additional', 'affiliation': []}, {'given': 'Greg N.', 'family': 'Brooke', 'sequence': 'additional', 'affiliation': []}], 'member': '1968', 'published-online': {'date-parts': [[2022, 12, 7]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '181', 'DOI': '10.1038/s41579-018-0118-9', 'article-title': 'Origin and evolution of pathogenic coronaviruses', 'volume': '17', 'author': 'Cui', 'year': '2019', 'journal-title': 'Nat. 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