Analgesics
Antiandrogens
Antihistamines
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
PPIs
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 researchAntiandrogensAntiandrogens (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta PPIs Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Use of Antiandrogens as Therapeutic Agents in COVID-19 Patients

Giotis et al., Viruses, doi:10.3390/v14122728
Dec 2022  
  Post
  Facebook
Share
  Source   PDF   All Studies   Meta AnalysisMeta
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. * >10% efficacy, ≥3 studies.
5,000+ studies for 104 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).
This PaperAntiandrogensAll
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.
References
Adjei, Hong, Molinari, Bull-Otterson, Ajani et al., Mortality risk among patients hospitalized primarily for COVID-19 during the Omicron and Delta variant pandemic periods-United States, April 2020-June 2022, MMWR Morb. Mortal. Wkly. Rep, doi:10.15585/mmwr.mm7137a4
Al-Attar, Presnell, Peterson, Thomas, Lutz, The effect of sex on immune cells in healthy aging: Elderly women have more robust natural killer lymphocytes than do elderly men, Mech. Ageing Dev, doi:10.1016/j.mad.2016.04.001
Alpanes, Fernandez-Duran, Escobar-Morreale, Androgens and polycystic ovary syndrome, Expert Rev. Endocrinol. Metab, doi:10.1586/eem.11.85
Alzain, Elbadwi, Alsamani, Discovery of novel TMPRSS2 inhibitors for COVID-19 using in silico fragment-based drug design, molecular docking, molecular dynamics, and quantum mechanics studies, Inform. Med. Unlocked, doi:10.1016/j.imu.2022.100870
Andrews, Tessier, Stowe, Gower, Kirsebom et al., Duration of protection against mild and severe disease by COVID-19 Vaccines, N. Engl. J. Med, doi:10.1056/NEJMoa2115481
Anestis, Zoi, Papavassiliou, Karamouzis, Androgen receptor in breast cancer-clinical and preclinical research insights, Molecules, doi:10.3390/molecules25020358
Antonelli, Penfold, Merino, Sudre, Molteni et al., Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: A prospective, community-based, nested, case-control study, Lancet Infect Dis, doi:10.1016/S1473-3099(21)00460-6
Antonelli, Pujol, Spector, Ourselin, Steves, Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2, Lancet, doi:10.1016/S0140-6736(22)00941-2
Baratchian, Mcmanus, Berk, Nakamura, Mukhopadhyay et al., Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications for sex-discordant COVID-19 outcomes, Sci. Rep, doi:10.1038/s41598-021-90491-1
Bayati, Kumar, Francis, Mcpherson, SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis, J. Biol. Chem, doi:10.1016/j.jbc.2021.100306
Beigel, Tomashek, Dodd, Mehta, Zingman et al., Remdesivir for the treatment of COVID-19-Final report, N. Engl. J. Med, doi:10.1056/NEJMoa2007764
Belouzard, Millet, Licitra, Whittaker, Mechanisms of coronavirus cell entry mediated by the viral spike protein, Viruses, doi:10.3390/v4061011
Bestle, Heindl, Limburg, Van Lam Van, Pilgram et al., TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells, Life Sci. Alliance, doi:10.26508/lsa.202000786
Bleach, Mcilroy, The divergent function of androgen receptor in breast cancer; analysis of steroid mediators and tumor intracrinology, Front. Endocrinol, doi:10.3389/fendo.2018.00594
Bouman, Heineman, Faas, Sex hormones and the immune response in humans, Hum. Reprod. Update, doi:10.1093/humupd/dmi008
Brightling, Evans, Long COVID: Which symptoms can be attributed to SARS-CoV-2 infection?, Lancet, doi:10.1016/S0140-6736(22)01385-X
Brooke, Bevan, The role of androgen receptor mutations in prostate cancer progression, Current Genom, doi:10.2174/138920209787581307
Brooke, Waxman, Bevan, The role of androgen receptor mutations in progression of prostate cancer
Calcagnile, Forgez, Iannelli, Bucci, Alifano et al., Molecular docking simulation reveals ACE2 polymorphisms that may increase the affinity of ACE2 with the SARS-CoV-2 spike protein, Biochimie, doi:10.1016/j.biochi.2020.11.004
Chakravarty, Nair, Hammouda, Ratnani, Gharib et al., Sex differences in SARS-CoV-2 infection rates and the potential link to prostate cancer, Commun. Biol, doi:10.1038/s42003-020-1088-9
Chen, Jiang, Xia, Liu, Yu et al., Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation, Aging Cell, doi:10.1111/acel.13168
Clinckemalie, Spans, Dubois, Laurent, Helsen et al., Androgen regulation of the TMPRSS2 gene and the effect of a SNP in an androgen response element, Mol. Endocrinol, doi:10.1210/me.2013-1098
Collin, Queen, Zerti, Dorgau, Georgiou et al., Co-expression of SARS-CoV-2 entry genes in the superficial adult human conjunctival, limbal and corneal epithelium suggests an additional route of entry via the ocular surface, Ocul. Surf, doi:10.1016/j.jtos.2020.05.013
Cui, Li, Shi, Origin and evolution of pathogenic coronaviruses, Nat. Rev. Microbiol, doi:10.1038/s41579-018-0118-9
Dart, Waxman, Aboagye, Bevan, Visualising androgen receptor activity in male and female mice, PLoS ONE, doi:10.1371/journal.pone.0071694
De Kloet, Krause, Woods, The renin angiotensin system and the metabolic syndrome, Physiol. Behav, doi:10.1016/j.physbeh.2010.03.018
Deng, Rasool, Russell, Natesan, Asangani, Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic strategy to combat COVID-19, iScience, doi:10.1016/j.isci.2021.102254
Doi, Ikeda, Hayase, Moriya, Morimura et al., Nafamostat mesylate treatment in combination with favipiravir for patients critically ill with COVID-19: A case series, Crit. Care, doi:10.1186/s13054-020-03078-z
Elrobaa, New, COVID-19: Pulmonary and extra pulmonary manifestations, Front. Public Health, doi:10.3389/fpubh.2021.711616
Esumi, Ishibashi, Yamaguchi, Nakajima, Tai et al., Transmembrane serine protease TMPRSS2 activates hepatitis C virus infection, Hepatology, doi:10.1002/hep.27426
Evans, Mcauley, Harrison, Shikotra, Singapuri et al., Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): A UK multicentre, prospective cohort study, Lancet Respir. Med, doi:10.1016/S2213-2600(21)00383-0
Fauci, Lane, Redfield, Covid-19-Navigating the uncharted, N. Engl. J. Med, doi:10.1056/NEJMe2002387
Feikin, Abu-Raddad, Andrews, Davies, Higdon et al., Assessing vaccine effectiveness against severe COVID-19 disease caused by omicron variant. Report from a meeting of the World Health Organization, Vaccine, doi:10.1016/j.vaccine.2022.04.069
Feng, He, Androgen receptor signaling in the development of castration-resistant prostate cancer, Front. Oncol, doi:10.3389/fonc.2019.00858
Fernandez-De-Las-Penas, De-La-Llave-Rincon, Ortega-Santiago, Ambite-Quesada, Gomez-Mayordomo et al., Prevalence and risk factors of musculoskeletal pain symptoms as long-term post-COVID sequelae in hospitalized COVID-19 survivors: A multicenter study, Pain, doi:10.1097/j.pain.0000000000002564
Fioretti, Sita-Lumsden, Bevan, Brooke, Revising the role of the androgen receptor in breast cancer, J. Mol. Endocrinol, doi:10.1530/JME-14-0030
Fish, The X-files in immunity: Sex-based differences predispose immune responses, Nat. Rev. Immunol, doi:10.1038/nri2394
Foo, Nakagawa, Rhodes, Simmons, The effects of sex hormones on immune function: A meta-analysis, Biol. Rev. Camb. Philos. Soc, doi:10.1111/brv.12243
Gierer, Bertram, Kaup, Wrensch, Heurich et al., The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies, J. Virol, doi:10.1128/JVI.00128-13
Gilliver, Sex steroids as inflammatory regulators, J. Steroid. Biochem. Mol. Biol, doi:10.1016/j.jsbmb.2009.12.015
Giotis, Carnell, Young, Ghanny, Soteropoulos et al., Entry of the bat influenza H17N10 virus into mammalian cells is enabled by the MHC class II HLA-DR receptor, Nat. Microbiol, doi:10.1038/s41564-019-0517-3
Greenhalgh, Sivan, Delaney, Evans, Milne, Long COVID-an update for primary care, BMJ, doi:10.1136/bmj-2022-072117
Group, Horby, Lim, Emberson, Mafham et al., Dexamethasone in hospitalized patients with COVID-19, N. Engl. J. Med
Gunst, Staerke, Pahus, Kristensen, Bodilsen et al., Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with COVID-19-A double-blind randomized controlled trial, EClinicalMedicine, doi:10.1016/j.eclinm.2021.100849
Henderson, Canna, Schulert, Volpi, Lee et al., On the alert for cytokine storm: Immunopathology in COVID-19, Arthritis Rheumatol, doi:10.1002/art.41285
Hoffmann, Kleine-Weber, Schroeder, Kruger, Herrler et al., SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell, doi:10.1016/j.cell.2020.02.052
Hofmann-Winkler, Moerer, Alt-Epping, Brauer, Buttner et al., Camostat mesylate may reduce severity of coronavirus disease 2019 sepsis: A first observation, Crit. Care Explor, doi:10.1097/CCE.0000000000000284
Hu, Shrimp, Guo, Xu, Chen et al., Discovery of TMPRSS2 inhibitors from virtual screening as a potential treatment of COVID-19, ACS Pharmacol. Transl. Sci, doi:10.1021/acsptsci.0c00221
Huang, Li, Gu, Zhang, Ren et al., Health outcomes in people 2 years after surviving hospitalisation with COVID-19: A longitudinal cohort study, Lancet Respir. Med, doi:10.1016/S2213-2600(22)00126-6
Ibrahim, Abdelmalek, Elshahat, Elfiky, COVID-19 spike-host cell receptor GRP78 binding site prediction, J. Infect, doi:10.1016/j.jinf.2020.02.026
Ioannidis, Axfors, Contopoulos-Ioannidis, Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters, Environ. Res, doi:10.1016/j.envres.2020.109890
Irham, Chou, Calkins, Adikusuma, Hsieh et al., Genetic variants that influence SARS-CoV-2 receptor TMPRSS2 expression among population cohorts from multiple continents, Biochem. Biophys. Res. Commun, doi:10.1016/j.bbrc.2020.05.179
Iwata-Yoshikawa, Okamura, Shimizu, Hasegawa, Takeda et al., TMPRSS2 contributes to virus spread and immunopathology in the airways of murine models after coronavirus infection, J. Virol, doi:10.1128/JVI.01815-18
Jackson, Farzan, Chen, Choe, Mechanisms of SARS-CoV-2 entry into cells, Nat. Rev. Mol. Cell Biol, doi:10.1038/s41580-021-00418-x
Jang, Rhee, Three cases of treatment with nafamostat in elderly patients with COVID-19 pneumonia who need oxygen therapy, Int. J. Infect. Dis, doi:10.1016/j.ijid.2020.05.072
Jia, Neptune, Cui, Targeting ACE2 for COVID-19 Therapy: Opportunities and challenges, Am. J. Respir. Cell Mol. Biol, doi:10.1165/rcmb.2020-0322PS
Jia, Pulmonary angiotensin-converting enzyme 2 (ACE2) and inflammatory lung disease, Shock, doi:10.1097/SHK.0000000000000633
Jin, Bai, He, Wu, Liu et al., Gender differences in patients with COVID-19: Focus on severity and mortality, Front. Public Health, doi:10.3389/fpubh.2020.00152
Joshi, Tyagi, Nigam, Molecular Level dissection of critical spike mutations in SARS-CoV-2 variants of concern (VOCs): A simplified review, ChemistrySelect, doi:10.1002/slct.202102074
Katopodis, Kerslake, Davies, Randeva, Chatha et al., COVID-19 and SARS-CoV-2 host cell entry mediators: Expression profiling of TMRSS4 in health and disease, Int. J. Mol. Med, doi:10.3892/ijmm.2021.4897
Khan, Ansar Ahmed, The immune System is a natural target for estrogen action: Opposing effects of estrogen in two prototypical autoimmune diseases, Front. Immunol, doi:10.3389/fimmu.2015.00635
Khoury, Docken, Subbarao, Kent, Davenport et al., Predicting the efficacy of variant-modified COVID-19 vaccine boosters, bioRxiv, doi:10.1101/2022.08.25.22279237
Kim, Heinlein, Hackman, Nelson, Phenotypic analysis of mice lacking the TMPRSS2-encoded protease, Mol. Cell Biol, doi:10.1128/MCB.26.3.965-975.2006
Klein, Flanagan, Sex differences in immune responses, Nat. Rev. Immunol, doi:10.1038/nri.2016.90
Klein, Hodgson, Robinson, Mechanisms of sex disparities in influenza pathogenesis, J. Leukoc. Biol, doi:10.1189/jlb.0811427
Klein, Huber, Sex differences in susceptibility to viral infection
Klein, Sex differences in prophylaxis and therapeutic treatments for viral diseases, Handb. Exp. Pharmacol
Kumar, Faiq, Pareek, Raza, Narayan et al., Relevance of SARS-CoV-2 related factors ACE2 and TMPRSS2 expressions in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients, Med. Hypotheses, doi:10.1016/j.mehy.2020.110271
Lanz, Bennamoun, Macek, Cathelineau, Sanchez-Salas, The importance of antiandrogen in prostate cancer treatment, Ann. Transl. Med, doi:10.21037/atm.2019.09.53
Leach, Mohr, Giotis, Cil, Isac et al., The antiandrogen enzalutamide downregulates TMPRSS2 and reduces cellular entry of SARS-CoV-2 in human lung cells, Nat. Commun, doi:10.1038/s41467-021-24342-y
Lee, Heberer, Gao, Becker, Loeb et al., A population-level analysis of the protective effects of androgen deprivation therapy against COVID-19 disease incidence and severity, Front. Med, doi:10.3389/fmed.2022.774773
Lee, Perl, Steiner, Pasternack, Li et al., neurovascular injury with complement activation and inflammation in COVID-19, Brain, doi:10.1093/brain/awac151
Lelis, Freitas, Machado, Crespo, Santos, Angiotensin-(1-7), adipokines and inflammation, Metabolism, doi:10.1016/j.metabol.2019.03.006
Li, Han, Dai, Xu, He et al., Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide, doi:10.1038/s41467-021-21171-x
Li, Huang, Wang, Wang, Liang et al., COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis, J. Med. Virol, doi:10.1002/jmv.25757
Liao, Huang, Xiao, Gu, Ouyang et al., Estrogen signaling effects on muscle-specific immune responses through controlling the recruitment and function of macrophages and T cells, Skelet Muscle, doi:10.1186/s13395-019-0205-2
Libert, Dejager, Pinheiro, The X chromosome in immune functions: When a chromosome makes the difference, Nat. Rev. Immunol, doi:10.1038/nri2815
Limburg, Harbig, Bestle, Stein, Moulton et al., TMPRSS2 is the major activating protease of influenza A virus in primary human airway cells and influenza B virus in human type II pneumocytes, J. Virol, doi:10.1128/JVI.00649-19
Lin, Ferguson, White, Wang, Vessella et al., Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2, Cancer Res
Long, Mistry, Haslam, Barclay, Host and viral determinants of influenza A virus species specificity, Nat. Rev. Microbiol, doi:10.1038/s41579-018-0115-z
Lucas, Heinlein, Kim, Hernandez, Malik et al., The androgen-regulated protease TMPRSS2 activates a proteolytic cascade involving components of the tumor microenvironment and promotes prostate cancer metastasis, Cancer Discov, doi:10.1158/2159-8290.CD-13-1010
Lukassen, Chua, Trefzer, Kahn, Schneider et al., SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells, EMBO J, doi:10.15252/embj.2020105114
Luttens, Gullberg, Abdurakhmanov, Vo, Akaberi et al., Ultralarge virtual screening identifies SARS-CoV-2 main protease inhibitors with broad-spectrum activity against coronaviruses, J. Am. Chem. Soc, doi:10.1021/jacs.1c08402
Mackin, Edwards, Atuk, Beltrami, Condon et al., Structure/function analysis of truncated amino-terminal ACE2 peptide analogs that bind to SARS-CoV-2 spike glycoprotein, Molecules, doi:10.3390/molecules27072070
Mahgoub, Alnaem, Fadlelmola, Abo-Idris, Makki et al., Discovery of novel potential inhibitors of TMPRSS2 and Mpro of SARS-CoV-2 using E-pharmacophore and docking-based virtual screening combined with molecular dynamic and quantum mechanics, J. Biomol. Struct. Dyn, doi:10.1080/07391102.2022.2112080
Mahoney, Damalanka, Tartell, Chung, Lourenco et al., A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and MERS-CoV viral entry and protect human epithelial lung cells, Proc. Natl. Acad. Sci, doi:10.1073/pnas.2108728118
Manandhar, Pai, Krishnamurthy, Kiran, Kumari, Identification, virtual screening and molecular dynamic analysis of novel TMPRSS2 inhibitors from natural compound database as potential entry-blocking agents in SARS-CoV-2 therapy, Struct. Chem, doi:10.1007/s11224-022-01991-3
Matsuyama, Nagata, Shirato, Kawase, Takeda et al., Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2, J. Virol, doi:10.1128/JVI.01542-10
Mauvais-Jarvis, Do anti-androgens have potential as therapeutics for COVID-19?, Endocrinology, doi:10.1210/endocr/bqab114
Mccoy, Cadegiani, Wambier, Herrera, Vano-Galvan et al., 5-alpha-reductase inhibitors are associated with reduced frequency of COVID-19 symptoms in males with androgenetic alopecia, J. Eur. Acad. Dermatol. Venereol, doi:10.1111/jdv.17021
Mcmanus, Gaston, Zein, Sharifi, Association Between Asthma and Reduced Androgen Receptor Expression in Airways, J. Endocr. Soc, doi:10.1210/jendso/bvac047
Mikkonen, Pihlajamaa, Sahu, Zhang, Janne, Androgen receptor and androgen-dependent gene expression in lung, Mol. Cell Endocrinol, doi:10.1016/j.mce.2009.12.022
Montazersaheb, Hosseiniyan Khatibi, Hejazi, Tarhriz, Farjami et al., COVID-19 infection: An overview on cytokine storm and related interventions, Virol. J, doi:10.1186/s12985-022-01814-1
Monteil, Dyczynski, Lauschke, Kwon, Wirnsberger et al., Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 infection, EMBO Mol. Med, doi:10.15252/emmm.202013426
Montopoli, Zumerle, Vettor, Rugge, Zorzi et al., Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: A population-based study (N = 4532), Ann. Oncol, doi:10.1016/j.annonc.2020.04.479
Nickols, Mi, Dematt, Biswas, Clise et al., Effect of androgen suppression on clinical outcomes in hospitalized men with COVID-19: The HITCH randomized clinical trial, JAMA Netw. Open, doi:10.1001/jamanetworkopen.2022.7852
Oertelt-Prigione, The influence of sex and gender on the immune response, Autoimmun. Rev, doi:10.1016/j.autrev.2011.11.022
Papadatos-Pastos, Dedes, De Bono, Kaye, Revisiting the role of antiandrogen strategies in ovarian cancer, Oncologist, doi:10.1634/theoncologist.2011-0164
Patel, Zhong, Liaw, Tremblay, Tsao et al., Does androgen deprivation therapy protect against severe complications from COVID-19?, Ann. Oncol, doi:10.1016/j.annonc.2020.06.023
Peacock, Brown, Zhou, Thakur, Sukhova et al., The altered entry pathway and antigenic distance of the SARS-CoV-2 Omicron variant map to separate domains of spike protein, bioRxiv, doi:10.1101/2021.12.31.474653
Plante, Mitchell, Plante, Debbink, Weaver et al., The variant gambit: COVID-19's next move, Cell Host Microbe, doi:10.1016/j.chom.2021.02.020
Punjani, Flannigan, Androgens and COVID-19: Exploring the role of testosterone replacement therapy, Int. J. Impot. Res, doi:10.1038/s41443-021-00524-6
Rahbar Saadat, Hosseiniyan Khatibi, Zununi Vahed, Ardalan, Host serine proteases: A potential targeted therapy for COVID-19 and influenza, Front. Mol. Biosci, doi:10.3389/fmolb.2021.725528
Rahman, Basharat, Yousuf, Castaldo, Rastrelli et al., Virtual screening of natural products against Type II transmembrane serine protease (TMPRSS2), the priming agent of coronavirus 2 (SARS-CoV-2), Molecules, doi:10.3390/molecules25102271
Rockx, Kuiken, Herfst, Bestebroer, Lamers et al., Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model, Science, doi:10.1126/science.abb7314
Rubin, From positive to negative to positive again-The mystery of why COVID-19 rebounds in some Patients who take paxlovid, JAMA, doi:10.1001/jama.2022.9925
Ruggieri, Gagliardi, Anticoli, Sex-dependent outcome of Hepatitis B and C viruses infections: Synergy of sex hormones and immune responses? Front, Immunol, doi:10.3389/fimmu.2018.02302
Samavati, Uhal, ACE2, much more than just a receptor for SARS-COV-2, Front. Cell Infect. Microbiol, doi:10.3389/fcimb.2020.00317
Shang, Wan, Luo, Ye, Geng et al., Cell entry mechanisms of SARS-CoV-2, Proc. Natl. Acad. Sci, doi:10.1073/pnas.2003138117
Shapira, Monreal, Dion, Buchholz, Imbiakha et al., A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and therapeutic, Nature, doi:10.1038/s41586-022-04661-w
Sharif-Askari, Saheb Sharif-Askari, Alabed, Temsah, Al Heialy et al., Airways expression of SARS-CoV-2 receptor, ACE2, and TMPRSS2 is lower in children than adults and increases with smoking and COPD, Mol. Ther. Methods Clin. Dev, doi:10.1016/j.omtm.2020.05.013
Shen, Qian, Yu, Narva, Yu et al., Inhibition of Influenza A virus propagation by benzoselenoxanthenes stabilizing TMPRSS2 Gene G-quadruplex and hence down-regulating TMPRSS2 expression, Sci. Rep, doi:10.1038/s41598-020-64368-8
Shirato, Kawase, Matsuyama, Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2, J. Virol, doi:10.1128/JVI.01890-13
Shrestha, Foster, Rawlinson, Tedla, Bull, Evolution of the SARS-CoV-2 omicron variants BA.1 to BA.5: Implications for immune escape and transmission, Rev. Med. Virol, doi:10.1002/rmv.2381
Shulla, Heald-Sargent, Subramanya, Zhao, Perlman et al., A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry, J. Virol, doi:10.1128/JVI.02062-10
Singh, Choudhari, Nema, Khan, ACE2 and TMPRSS2 polymorphisms in various diseases with special reference to its impact on COVID-19 disease, Microb. Pathog, doi:10.1016/j.micpath.2020.104621
Stasi, Rastrelli, The role of sex hormones in the disparity of COVID-19 outcomes based on gender, J. Sex Med, doi:10.1016/j.jsxm.2021.09.003
Stopsack, Mucci, Antonarakis, Nelson, Kantoff, TMPRSS2 and COVID-19: Serendipity or opportunity for intervention?, Cancer Discov, doi:10.1158/2159-8290.CD-20-0451
Straub, The complex role of estrogens in inflammation, Endocr. Rev, doi:10.1210/er.2007-0001
Tallei, Alhumaid, Almusa, Fatimawali; Kusumawaty, Alynbiawi et al., Update on the omicron sub-variants BA.4 and BA.5, Rev. Med. Virol, doi:10.1002/rmv.2391
Taneja, Sex hormones determine immune response, Front. Immunol, doi:10.3389/fimmu.2018.01931
Tao, Tzou, Nouhin, Gupta, De Oliveira et al., The biological and clinical significance of emerging SARS-CoV-2 variants, Nat. Rev. Genet, doi:10.1038/s41576-021-00408-x
Tegally, Moir, Everatt, Giovanetti, Scheepers et al., Emergence of SARS-CoV-2 omicron lineages BA.4 and BA.5 in South Africa, Nat. Med, doi:10.1038/s41591-022-01911-2
Thompson, Natarajan, Irving, Rowley, Griggs et al., Effectiveness of a third dose of mRNA vaccines against COVID-19-associated emergency department and urgent care encounters and hospitalizations among adults during periods of Delta and Omicron variant predominance-VISION Network, 10 States, MMWR Morb. Mortal. Wkly. Rep
Tian, Kuo, Chen, Ou, Enhancement of hepatitis B virus replication by androgen and its receptor in mice, J. Virol, doi:10.1128/JVI.06707-11
Vaarala, Porvari, Kellokumpu, Kyllonen, Vihko, Expression of transmembrane serine protease TMPRSS2 in mouse and human tissues, J. Pathol, doi:10.1002/1096-9896(2000)9999:9999<::AID-PATH743>3.0.CO;2-T
Vangeel, Chiu, De Jonghe, Maes, Slechten et al., molnupiravir and nirmatrelvir remain active against SARS-CoV-2 omicron and other variants of concern, Antiviral Res, doi:10.1016/j.antiviral.2022.105252
Vom Steeg, Klein, Sex matters in infectious disease pathogenesis, PLoS Pathog, doi:10.1371/journal.ppat.1005374
Wang, Berger, Davis, Kaelber, Volkow et al., COVID-19 rebound after paxlovid and molnupiravir during, doi:10.1101/2022.06.21.22276724
Wang, Chiou, Poirion, Buchanan, Valdez et al., Single-cell multiomic profiling of human lungs reveals cell-type-specific and age-dynamic control of SARS-CoV-2 host genes, Elife, doi:10.7554/eLife.62522
Wang, Yang, Broad-spectrum prodrugs with anti-SARS-CoV-2 activities: Strategies, benefits, and challenges, J. Med. Virol, doi:10.1002/jmv.27517
Wang, Yang, Post-acute sequelae of SARS-CoV-2 infection: A neglected public health issue, Front. Public Health, doi:10.3389/fpubh.2022.908757
Wang, Yang, Zhao, Co-crystallization and structure determination: An effective direction for anti-SARS-CoV-2 drug discovery, Comput. Struct. Biotechnol. J, doi:10.1016/j.csbj.2021.08.029
Weinreich, Sivapalasingam, Norton, Ali, Gao et al., REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19, N. Engl. J. Med, doi:10.1056/NEJMoa2035002
Welen, Rosendal, Gisslen, Lenman, Freyhult et al., A Phase 2 Trial of the effect of antiandrogen therapy on COVID-19 outcome: No evidence of benefit, supported by epidemiology and in vitro data, Eur. Urol, doi:10.1016/j.eururo.2021.12.013
Wenham, Smith, Morgan, on behalf of the Gender and COVID-19 Working Group. COVID-19: The gendered impacts of the outbreak, Lancet, doi:10.1016/S0140-6736(20)30526-2
Whitaker, Elliott, Chadeau-Hyam, Riley, Darzi et al., Persistent COVID-19 symptoms in a community study of 606,434 people in England, Nat. Commun, doi:10.1038/s41467-022-29521-z
Willett, Grove, Maclean, Wilkie, De Lorenzo et al., SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway, Nat. Rev. Immunol, doi:10.1038/s41577-022-00681-9
Williamson, Walker, Bhaskaran, Bacon, Bates et al., Factors associated with COVID-19-related death using OpenSAFELY, Nature, doi:10.1038/s41586-020-2521-4
Xu, Chen, Yuan, Yi, Ding et al., Factors associated with prolonged viral RNA shedding in patients with coronavirus disease 2019 (COVID-19), Clin. Infect Dis, doi:10.1093/cid/ciaa351
Yadav, Chaudhary, Jain, Chaudhary, Khanra et al., Role of structural and non-structural proteins and therapeutic targets of SARS-CoV-2 for COVID-19, Cells, doi:10.3390/cells10040821
Yip, Sinclair, Antiandrogen therapy for androgenetic alopecia, Expert Rev. Dermatol, doi:10.1586/17469872.1.2.261
Zhang, Dong, Liu, Gao, Risk and protective factors for COVID-19 morbidity, severity, and mortality, Clin. Rev. Allergy Immunol, doi:10.1007/s12016-022-08921-5
Zhang, Penn, Barclay, Giotis, Naive human macrophages are refractory to SARS-CoV-2 infection and exhibit a modest inflammatory response early in infection, Viruses, doi:10.3390/v14020441
Zhang, Penninger, Li, Zhong, Slutsky, Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: Molecular mechanisms and potential therapeutic target, Intensive Care Med, doi:10.1007/s00134-020-05985-9
Zhang, Xie, Hashimoto, Current status of potential therapeutic candidates for the COVID-19 crisis, Brain Behav. Immun, doi:10.1016/j.bbi.2020.04.046
Zhu, Ji, Pang, Zhong, Li et al., Clinical characteristics of 3,062 COVID-19 patients: A meta-analysis, J. Med. Virol, doi:10.1002/jmv.25884
Zou, Chen, Zou, Han, Hao et al., Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection, Front. Med, doi:10.1007/s11684-020-0754-0
{ '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. Rev. Microbiol.'}, { 'key': 'ref_2', 'doi-asserted-by': 'crossref', 'first-page': '1182', 'DOI': '10.15585/mmwr.mm7137a4', 'article-title': 'Mortality risk among patients hospitalized primarily for COVID-19 ' 'during the Omicron and Delta variant pandemic periods-United States, ' 'April 2020–June 2022', 'volume': '71', 'author': 'Adjei', 'year': '2022', 'journal-title': 'MMWR Morb. Mortal. Wkly. Rep.'}, { 'key': 'ref_3', 'doi-asserted-by': 'crossref', 'first-page': '1902', 'DOI': '10.1002/jmv.25884', 'article-title': 'Clinical characteristics of 3,062 COVID-19 patients: A meta-analysis', 'volume': '92', 'author': 'Zhu', 'year': '2020', 'journal-title': 'J. Med. Virol.'}, { 'key': 'ref_4', 'doi-asserted-by': 'crossref', 'first-page': '1957', 'DOI': '10.1038/s41467-022-29521-z', 'article-title': 'Persistent COVID-19 symptoms in a community study of 606,434 people in ' 'England', 'volume': '13', 'author': 'Whitaker', 'year': '2022', 'journal-title': 'Nat. Commun.'}, { 'key': 'ref_5', 'doi-asserted-by': 'crossref', 'first-page': '1275', 'DOI': '10.1016/S2213-2600(21)00383-0', 'article-title': 'Physical, cognitive, and mental health impacts of COVID-19 after ' 'hospitalisation (PHOSP-COVID): A UK multicentre, prospective cohort ' 'study', 'volume': '9', 'author': 'Evans', 'year': '2021', 'journal-title': 'Lancet Respir. Med.'}, { 'key': 'ref_6', 'doi-asserted-by': 'crossref', 'unstructured': 'Zhang, Z., Penn, R., Barclay, W.S., and Giotis, E.S. (2022). Naive human ' 'macrophages are refractory to SARS-CoV-2 infection and exhibit a modest ' 'inflammatory response early in infection. Viruses, 14.', 'DOI': '10.3390/v14020441'}, { 'key': 'ref_7', 'doi-asserted-by': 'crossref', 'first-page': '92', 'DOI': '10.1186/s12985-022-01814-1', 'article-title': 'COVID-19 infection: An overview on cytokine storm and related ' 'interventions', 'volume': '19', 'author': 'Montazersaheb', 'year': '2022', 'journal-title': 'Virol. J.'}, { 'key': 'ref_8', 'doi-asserted-by': 'crossref', 'first-page': '1059', 'DOI': '10.1002/art.41285', 'article-title': 'On the alert for cytokine storm: Immunopathology in COVID-19', 'volume': '72', 'author': 'Henderson', 'year': '2020', 'journal-title': 'Arthritis Rheumatol.'}, { 'key': 'ref_9', 'doi-asserted-by': 'crossref', 'first-page': '711616', 'DOI': '10.3389/fpubh.2021.711616', 'article-title': 'COVID-19: Pulmonary and extra pulmonary manifestations', 'volume': '9', 'author': 'Elrobaa', 'year': '2021', 'journal-title': 'Front. Public Health'}, { 'key': 'ref_10', 'doi-asserted-by': 'crossref', 'first-page': '2555', 'DOI': '10.1093/brain/awac151', 'article-title': 'neurovascular injury with complement activation and inflammation in ' 'COVID-19', 'volume': '145', 'author': 'Lee', 'year': '2022', 'journal-title': 'Brain'}, { 'key': 'ref_11', 'doi-asserted-by': 'crossref', 'first-page': 'e072117', 'DOI': '10.1136/bmj-2022-072117', 'article-title': 'Long COVID-an update for primary care', 'volume': '378', 'author': 'Greenhalgh', 'year': '2022', 'journal-title': 'BMJ'}, { 'key': 'ref_12', 'doi-asserted-by': 'crossref', 'first-page': '411', 'DOI': '10.1016/S0140-6736(22)01385-X', 'article-title': 'Long COVID: Which symptoms can be attributed to SARS-CoV-2 infection?', 'volume': '400', 'author': 'Brightling', 'year': '2022', 'journal-title': 'Lancet'}, { 'key': 'ref_13', 'doi-asserted-by': 'crossref', 'first-page': '863', 'DOI': '10.1016/S2213-2600(22)00126-6', 'article-title': 'Health outcomes in people 2 years after surviving hospitalisation with ' 'COVID-19: A longitudinal cohort study', 'volume': '10', 'author': 'Huang', 'year': '2022', 'journal-title': 'Lancet Respir. Med.'}, { 'key': 'ref_14', 'doi-asserted-by': 'crossref', 'first-page': '908757', 'DOI': '10.3389/fpubh.2022.908757', 'article-title': 'Post-acute sequelae of SARS-CoV-2 infection: A neglected public health ' 'issue', 'volume': '10', 'author': 'Wang', 'year': '2022', 'journal-title': 'Front. Public Health'}, { 'key': 'ref_15', 'doi-asserted-by': 'crossref', 'first-page': '3516', 'DOI': '10.1016/j.vaccine.2022.04.069', 'article-title': 'Assessing vaccine effectiveness against severe COVID-19 disease caused ' 'by omicron variant. Report from a meeting of the World Health ' 'Organization', 'volume': '40', 'author': 'Feikin', 'year': '2022', 'journal-title': 'Vaccine'}, { 'key': 'ref_16', 'doi-asserted-by': 'crossref', 'first-page': '340', 'DOI': '10.1056/NEJMoa2115481', 'article-title': 'Duration of protection against mild and severe disease by COVID-19 ' 'Vaccines', 'volume': '386', 'author': 'Andrews', 'year': '2022', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref_17', 'doi-asserted-by': 'crossref', 'first-page': 'e2381', 'DOI': '10.1002/rmv.2381', 'article-title': 'Evolution of the SARS-CoV-2 omicron variants BA.1 to BA.5: Implications ' 'for immune escape and transmission', 'volume': '32', 'author': 'Shrestha', 'year': '2022', 'journal-title': 'Rev. Med. Virol.'}, { 'key': 'ref_18', 'doi-asserted-by': 'crossref', 'first-page': '7981', 'DOI': '10.1002/slct.202102074', 'article-title': 'Molecular Level dissection of critical spike mutations in SARS-CoV-2 ' 'variants of concern (VOCs): A simplified review', 'volume': '6', 'author': 'Joshi', 'year': '2021', 'journal-title': 'ChemistrySelect'}, { 'key': 'ref_19', 'doi-asserted-by': 'crossref', 'first-page': '757', 'DOI': '10.1038/s41576-021-00408-x', 'article-title': 'The biological and clinical significance of emerging SARS-CoV-2 ' 'variants', 'volume': '22', 'author': 'Tao', 'year': '2021', 'journal-title': 'Nat. Rev. Genet.'}, { 'key': 'ref_20', 'doi-asserted-by': 'crossref', 'first-page': '508', 'DOI': '10.1016/j.chom.2021.02.020', 'article-title': 'The variant gambit: COVID-19’s next move', 'volume': '29', 'author': 'Plante', 'year': '2021', 'journal-title': 'Cell Host Microbe'}, { 'key': 'ref_21', 'doi-asserted-by': 'crossref', 'first-page': '1785', 'DOI': '10.1038/s41591-022-01911-2', 'article-title': 'Emergence of SARS-CoV-2 omicron lineages BA.4 and BA.5 in South Africa', 'volume': '28', 'author': 'Tegally', 'year': '2022', 'journal-title': 'Nat. Med.'}, { 'key': 'ref_22', 'first-page': 'e2391', 'article-title': 'Update on the omicron sub-variants BA.4 and BA.5', 'volume': '26', 'author': 'Tallei', 'year': '2022', 'journal-title': 'Rev. Med. Virol.'}, { 'key': 'ref_23', 'doi-asserted-by': 'crossref', 'first-page': '139', 'DOI': '10.15585/mmwr.mm7104e3', 'article-title': 'Effectiveness of a third dose of mRNA vaccines against ' 'COVID-19-associated emergency department and urgent care encounters and ' 'hospitalizations among adults during periods of Delta and Omicron ' 'variant predominance-VISION Network, 10 States, August 2021–January ' '2022', 'volume': '71', 'author': 'Thompson', 'year': '2022', 'journal-title': 'MMWR Morb. Mortal. Wkly. Rep.'}, { 'key': 'ref_24', 'doi-asserted-by': 'crossref', 'unstructured': 'Khoury, D.S., Docken, S.S., Subbarao, K., Kent, S.J., Davenport, M.P., ' 'and Cromer, D. (2022). Predicting the efficacy of variant-modified ' 'COVID-19 vaccine boosters. bioRxiv.', 'DOI': '10.1101/2022.08.25.22279237'}, { 'key': 'ref_25', 'doi-asserted-by': 'crossref', 'first-page': '238', 'DOI': '10.1056/NEJMoa2035002', 'article-title': 'REGN-COV2, a neutralizing antibody cocktail, in outpatients with ' 'Covid-19', 'volume': '384', 'author': 'Weinreich', 'year': '2021', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref_26', 'doi-asserted-by': 'crossref', 'first-page': '693', 'DOI': '10.1056/NEJMoa2021436', 'article-title': 'Dexamethasone in hospitalized patients with COVID-19', 'volume': '384', 'author': 'Group', 'year': '2021', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref_27', 'doi-asserted-by': 'crossref', 'first-page': '1813', 'DOI': '10.1056/NEJMoa2007764', 'article-title': 'Remdesivir for the treatment of COVID-19-Final report', 'volume': '383', 'author': 'Beigel', 'year': '2020', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref_28', 'doi-asserted-by': 'crossref', 'first-page': '105252', 'DOI': '10.1016/j.antiviral.2022.105252', 'article-title': 'Remdesivir, molnupiravir and nirmatrelvir remain active against ' 'SARS-CoV-2 omicron and other variants of concern', 'volume': '198', 'author': 'Vangeel', 'year': '2022', 'journal-title': 'Antiviral Res.'}, { 'key': 'ref_29', 'doi-asserted-by': 'crossref', 'unstructured': 'WHO Solidarity Trial Consortium (2022). Remdesivir and three other drugs ' 'for hospitalised patients with COVID-19: Final results of the WHO ' 'Solidarity randomised trial and updated meta-analyses. Lancet, 399, ' '1941–1953.', 'DOI': '10.1016/S0140-6736(22)00519-0'}, { 'key': 'ref_30', 'doi-asserted-by': 'crossref', 'unstructured': 'Wang, L., Berger, N.A., Davis, P.B., Kaelber, D.C., Volkow, N.D., and ' 'Xu, R. (2022). COVID-19 rebound after paxlovid and molnupiravir during ' 'January–June 2022. medRxiv.', 'DOI': '10.1101/2022.06.21.22276724'}, { 'key': 'ref_31', 'doi-asserted-by': 'crossref', 'first-page': '2380', 'DOI': '10.1001/jama.2022.9925', 'article-title': 'From positive to negative to positive again-The mystery of why COVID-19 ' 'rebounds in some Patients who take paxlovid', 'volume': '327', 'author': 'Rubin', 'year': '2022', 'journal-title': 'JAMA'}, { 'key': 'ref_32', 'doi-asserted-by': 'crossref', 'first-page': '577', 'DOI': '10.1002/jmv.25757', 'article-title': 'COVID-19 patients’ clinical characteristics, discharge rate, and ' 'fatality rate of meta-analysis', 'volume': '92', 'author': 'Li', 'year': '2020', 'journal-title': 'J. Med. Virol.'}, { 'key': 'ref_33', 'doi-asserted-by': 'crossref', 'first-page': '109890', 'DOI': '10.1016/j.envres.2020.109890', 'article-title': 'Population-level COVID-19 mortality risk for non-elderly individuals ' 'overall and for non-elderly individuals without underlying diseases in ' 'pandemic epicenters', 'volume': '188', 'author': 'Ioannidis', 'year': '2020', 'journal-title': 'Environ. Res.'}, { 'key': 'ref_34', 'doi-asserted-by': 'crossref', 'first-page': '430', 'DOI': '10.1038/s41586-020-2521-4', 'article-title': 'Factors associated with COVID-19-related death using OpenSAFELY', 'volume': '584', 'author': 'Williamson', 'year': '2020', 'journal-title': 'Nature'}, { 'key': 'ref_35', 'doi-asserted-by': 'crossref', 'first-page': '1268', 'DOI': '10.1056/NEJMe2002387', 'article-title': 'Covid-19-Navigating the uncharted', 'volume': '382', 'author': 'Fauci', 'year': '2020', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref_36', 'first-page': '1', 'article-title': 'Risk and protective factors for COVID-19 morbidity, severity, and ' 'mortality', 'volume': '19', 'author': 'Zhang', 'year': '2022', 'journal-title': 'Clin. Rev. Allergy Immunol.'}, { 'key': 'ref_37', 'doi-asserted-by': 'crossref', 'first-page': '2263', 'DOI': '10.1016/S0140-6736(22)00941-2', 'article-title': 'Risk of long COVID associated with delta versus omicron variants of ' 'SARS-CoV-2', 'volume': '399', 'author': 'Antonelli', 'year': '2022', 'journal-title': 'Lancet'}, { 'key': 'ref_38', 'doi-asserted-by': 'crossref', 'first-page': '43', 'DOI': '10.1016/S1473-3099(21)00460-6', 'article-title': 'Risk factors and disease profile of post-vaccination SARS-CoV-2 ' 'infection in UK users of the COVID Symptom Study app: A prospective, ' 'community-based, nested, case-control study', 'volume': '22', 'author': 'Antonelli', 'year': '2022', 'journal-title': 'Lancet Infect Dis.'}, { 'key': 'ref_39', 'doi-asserted-by': 'crossref', 'first-page': 'e989', 'DOI': '10.1097/j.pain.0000000000002564', 'article-title': 'Prevalence and risk factors of musculoskeletal pain symptoms as ' 'long-term post-COVID sequelae in hospitalized COVID-19 survivors: A ' 'multicenter study', 'volume': '163', 'author': 'Cuadrado', 'year': '2022', 'journal-title': 'Pain'}, { 'key': 'ref_40', 'doi-asserted-by': 'crossref', 'first-page': '846', 'DOI': '10.1016/S0140-6736(20)30526-2', 'article-title': 'COVID-19: The gendered impacts of the outbreak', 'volume': '395', 'author': 'Wenham', 'year': '2020', 'journal-title': 'Lancet'}, { 'key': 'ref_41', 'doi-asserted-by': 'crossref', 'first-page': '1950', 'DOI': '10.1016/j.jsxm.2021.09.003', 'article-title': 'The role of sex hormones in the disparity of COVID-19 outcomes based on ' 'gender', 'volume': '18', 'author': 'Stasi', 'year': '2021', 'journal-title': 'J. Sex Med.'}, { 'key': 'ref_42', 'doi-asserted-by': 'crossref', 'first-page': '152', 'DOI': '10.3389/fpubh.2020.00152', 'article-title': 'Gender differences in patients with COVID-19: Focus on severity and ' 'mortality', 'volume': '8', 'author': 'Jin', 'year': '2020', 'journal-title': 'Front. Public Health'}, { 'key': 'ref_43', 'doi-asserted-by': 'crossref', 'first-page': '799', 'DOI': '10.1093/cid/ciaa351', 'article-title': 'Factors associated with prolonged viral RNA shedding in patients with ' 'coronavirus disease 2019 (COVID-19)', 'volume': '71', 'author': 'Xu', 'year': '2020', 'journal-title': 'Clin. Infect Dis.'}, { 'key': 'ref_44', 'doi-asserted-by': 'crossref', 'first-page': '374', 'DOI': '10.1038/s42003-020-1088-9', 'article-title': 'Sex differences in SARS-CoV-2 infection rates and the potential link to ' 'prostate cancer', 'volume': '3', 'author': 'Chakravarty', 'year': '2020', 'journal-title': 'Commun. Biol.'}, { 'key': 'ref_45', 'doi-asserted-by': 'crossref', 'unstructured': 'Klein, S.L., and Roberts, C. (2010). Sex Hormones and Immunity to ' 'Infection, Springer.', 'DOI': '10.1007/978-3-642-02155-8'}, { 'key': 'ref_46', 'doi-asserted-by': 'crossref', 'first-page': '67', 'DOI': '10.1189/jlb.0811427', 'article-title': 'Mechanisms of sex disparities in influenza pathogenesis', 'volume': '92', 'author': 'Klein', 'year': '2012', 'journal-title': 'J. Leukoc. Biol.'}, { 'key': 'ref_47', 'doi-asserted-by': 'crossref', 'unstructured': 'Klein, S.L. (2012). Sex differences in prophylaxis and therapeutic ' 'treatments for viral diseases. Handb. Exp. Pharmacol., 499–522.', 'DOI': '10.1007/978-3-642-30726-3_22'}, { 'key': 'ref_48', 'doi-asserted-by': 'crossref', 'first-page': '626', 'DOI': '10.1038/nri.2016.90', 'article-title': 'Sex differences in immune responses', 'volume': '16', 'author': 'Klein', 'year': '2016', 'journal-title': 'Nat. Rev. Immunol.'}, { 'key': 'ref_49', 'doi-asserted-by': 'crossref', 'first-page': '20', 'DOI': '10.1186/s13395-019-0205-2', 'article-title': 'Estrogen signaling effects on muscle-specific immune responses through ' 'controlling the recruitment and function of macrophages and T cells', 'volume': '9', 'author': 'Liao', 'year': '2019', 'journal-title': 'Skelet Muscle'}, { 'key': 'ref_50', 'doi-asserted-by': 'crossref', 'first-page': '25', 'DOI': '10.1016/j.mad.2016.04.001', 'article-title': 'The effect of sex on immune cells in healthy aging: Elderly women have ' 'more robust natural killer lymphocytes than do elderly men', 'volume': '156', 'author': 'Presnell', 'year': '2016', 'journal-title': 'Mech. Ageing Dev.'}, { 'key': 'ref_51', 'doi-asserted-by': 'crossref', 'first-page': '737', 'DOI': '10.1038/nri2394', 'article-title': 'The X-files in immunity: Sex-based differences predispose immune ' 'responses', 'volume': '8', 'author': 'Fish', 'year': '2008', 'journal-title': 'Nat. Rev. Immunol.'}, { 'key': 'ref_52', 'doi-asserted-by': 'crossref', 'first-page': '594', 'DOI': '10.1038/nri2815', 'article-title': 'The X chromosome in immune functions: When a chromosome makes the ' 'difference', 'volume': '10', 'author': 'Libert', 'year': '2010', 'journal-title': 'Nat. Rev. Immunol.'}, { 'key': 'ref_53', 'doi-asserted-by': 'crossref', 'unstructured': 'vom Steeg, L.G., and Klein, S.L. (2016). Sex matters in infectious ' 'disease pathogenesis. PLoS Pathog., 12.', 'DOI': '10.1371/journal.ppat.1005374'}, { 'key': 'ref_54', 'doi-asserted-by': 'crossref', 'first-page': 'A479', 'DOI': '10.1016/j.autrev.2011.11.022', 'article-title': 'The influence of sex and gender on the immune response', 'volume': '11', 'year': '2012', 'journal-title': 'Autoimmun. Rev.'}, { 'key': 'ref_55', 'doi-asserted-by': 'crossref', 'first-page': '521', 'DOI': '10.1210/er.2007-0001', 'article-title': 'The complex role of estrogens in inflammation', 'volume': '28', 'author': 'Straub', 'year': '2007', 'journal-title': 'Endocr. Rev.'}, { 'key': 'ref_56', 'doi-asserted-by': 'crossref', 'first-page': '105', 'DOI': '10.1016/j.jsbmb.2009.12.015', 'article-title': 'Sex steroids as inflammatory regulators', 'volume': '120', 'author': 'Gilliver', 'year': '2010', 'journal-title': 'J. Steroid. Biochem. Mol. Biol.'}, { 'key': 'ref_57', 'first-page': '635', 'article-title': 'The immune System is a natural target for estrogen action: Opposing ' 'effects of estrogen in two prototypical autoimmune diseases', 'volume': '6', 'author': 'Khan', 'year': '2015', 'journal-title': 'Front. Immunol.'}, { 'key': 'ref_58', 'doi-asserted-by': 'crossref', 'first-page': '551', 'DOI': '10.1111/brv.12243', 'article-title': 'The effects of sex hormones on immune function: A meta-analysis', 'volume': '92', 'author': 'Foo', 'year': '2017', 'journal-title': 'Biol. Rev. Camb. Philos. Soc.'}, { 'key': 'ref_59', 'doi-asserted-by': 'crossref', 'first-page': '1931', 'DOI': '10.3389/fimmu.2018.01931', 'article-title': 'Sex hormones determine immune response', 'volume': '9', 'author': 'Taneja', 'year': '2018', 'journal-title': 'Front. Immunol.'}, { 'key': 'ref_60', 'doi-asserted-by': 'crossref', 'first-page': '411', 'DOI': '10.1093/humupd/dmi008', 'article-title': 'Sex hormones and the immune response in humans', 'volume': '11', 'author': 'Bouman', 'year': '2005', 'journal-title': 'Hum. Reprod. Update'}, { 'key': 'ref_61', 'doi-asserted-by': 'crossref', 'first-page': '2302', 'DOI': '10.3389/fimmu.2018.02302', 'article-title': 'Sex-dependent outcome of Hepatitis B and C viruses infections: Synergy ' 'of sex hormones and immune responses?', 'volume': '9', 'author': 'Ruggieri', 'year': '2018', 'journal-title': 'Front. Immunol.'}, { 'key': 'ref_62', 'doi-asserted-by': 'crossref', 'first-page': '1904', 'DOI': '10.1128/JVI.06707-11', 'article-title': 'Enhancement of hepatitis B virus replication by androgen and its ' 'receptor in mice', 'volume': '86', 'author': 'Tian', 'year': '2012', 'journal-title': 'J. Virol.'}, { 'key': 'ref_63', 'doi-asserted-by': 'crossref', 'first-page': '3', 'DOI': '10.1038/s41580-021-00418-x', 'article-title': 'Mechanisms of SARS-CoV-2 entry into cells', 'volume': '23', 'author': 'Jackson', 'year': '2022', 'journal-title': 'Nat. Rev. Mol. Cell Biol.'}, { 'key': 'ref_64', 'doi-asserted-by': 'crossref', 'unstructured': 'Yadav, R., Chaudhary, J.K., Jain, N., Chaudhary, P.K., Khanra, S., ' 'Dhamija, P., Sharma, A., Kumar, A., and Handu, S. (2021). Role of ' 'structural and non-structural proteins and therapeutic targets of ' 'SARS-CoV-2 for COVID-19. Cells, 10.', 'DOI': '10.3390/cells10040821'}, { 'key': 'ref_65', 'doi-asserted-by': 'crossref', 'first-page': '100306', 'DOI': '10.1016/j.jbc.2021.100306', 'article-title': 'SARS-CoV-2 infects cells after viral entry via clathrin-mediated ' 'endocytosis', 'volume': '296', 'author': 'Bayati', 'year': '2021', 'journal-title': 'J. Biol. Chem.'}, { 'key': 'ref_66', 'doi-asserted-by': 'crossref', 'first-page': '11727', 'DOI': '10.1073/pnas.2003138117', 'article-title': 'Cell entry mechanisms of SARS-CoV-2', 'volume': '117', 'author': 'Shang', 'year': '2020', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}, { 'key': 'ref_67', 'doi-asserted-by': 'crossref', 'first-page': '271', 'DOI': '10.1016/j.cell.2020.02.052', 'article-title': 'SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a ' 'clinically proven protease inhibitor', 'volume': '181', 'author': 'Hoffmann', 'year': '2020', 'journal-title': 'Cell'}, { 'key': 'ref_68', 'doi-asserted-by': 'crossref', 'first-page': '239', 'DOI': '10.1097/SHK.0000000000000633', 'article-title': 'Pulmonary angiotensin-converting enzyme 2 (ACE2) and inflammatory lung ' 'disease', 'volume': '46', 'author': 'Jia', 'year': '2016', 'journal-title': 'Shock'}, { 'key': 'ref_69', 'doi-asserted-by': 'crossref', 'first-page': '2035', 'DOI': '10.1038/s41564-019-0517-3', 'article-title': 'Entry of the bat influenza H17N10 virus into mammalian cells is enabled ' 'by the MHC class II HLA-DR receptor', 'volume': '4', 'author': 'Giotis', 'year': '2019', 'journal-title': 'Nat. Microbiol.'}, { 'key': 'ref_70', 'doi-asserted-by': 'crossref', 'first-page': '67', 'DOI': '10.1038/s41579-018-0115-z', 'article-title': 'Host and viral determinants of influenza A virus species specificity', 'volume': '17', 'author': 'Long', 'year': '2019', 'journal-title': 'Nat. Rev. Microbiol.'}, { 'key': 'ref_71', 'doi-asserted-by': 'crossref', 'first-page': '12658', 'DOI': '10.1128/JVI.01542-10', 'article-title': 'Efficient activation of the severe acute respiratory syndrome ' 'coronavirus spike protein by the transmembrane protease TMPRSS2', 'volume': '84', 'author': 'Matsuyama', 'year': '2010', 'journal-title': 'J. Virol.'}, { 'key': 'ref_72', 'doi-asserted-by': 'crossref', 'first-page': '873', 'DOI': '10.1128/JVI.02062-10', 'article-title': 'A transmembrane serine protease is linked to the severe acute ' 'respiratory syndrome coronavirus receptor and activates virus entry', 'volume': '85', 'author': 'Shulla', 'year': '2011', 'journal-title': 'J. Virol.'}, { 'key': 'ref_73', 'doi-asserted-by': 'crossref', 'first-page': '1011', 'DOI': '10.3390/v4061011', 'article-title': 'Mechanisms of coronavirus cell entry mediated by the viral spike ' 'protein', 'volume': '4', 'author': 'Belouzard', 'year': '2012', 'journal-title': 'Viruses'}, { 'key': 'ref_74', 'doi-asserted-by': 'crossref', 'first-page': '554', 'DOI': '10.1016/j.jinf.2020.02.026', 'article-title': 'COVID-19 spike-host cell receptor GRP78 binding site prediction', 'volume': '80', 'author': 'Ibrahim', 'year': '2020', 'journal-title': 'J. Infect.'}, { 'key': 'ref_75', 'first-page': '4180', 'article-title': 'Prostate-localized and androgen-regulated expression of the ' 'membrane-bound serine protease TMPRSS2', 'volume': '59', 'author': 'Lin', 'year': '1999', 'journal-title': 'Cancer Res.'}, { 'key': 'ref_76', 'doi-asserted-by': 'crossref', 'first-page': '1310', 'DOI': '10.1158/2159-8290.CD-13-1010', 'article-title': 'The androgen-regulated protease TMPRSS2 activates a proteolytic cascade ' 'involving components of the tumor microenvironment and promotes ' 'prostate cancer metastasis', 'volume': '4', 'author': 'Lucas', 'year': '2014', 'journal-title': 'Cancer Discov.'}, { 'key': 'ref_77', 'doi-asserted-by': 'crossref', 'first-page': '64', 'DOI': '10.3892/ijmm.2021.4897', 'article-title': 'COVID-19 and SARS-CoV-2 host cell entry mediators: Expression profiling ' 'of TMRSS4 in health and disease', 'volume': '47', 'author': 'Katopodis', 'year': '2021', 'journal-title': 'Int. J. Mol. Med.'}, { 'key': 'ref_78', 'doi-asserted-by': 'crossref', 'first-page': 'e105114', 'DOI': '10.15252/embj.2020105114', 'article-title': 'SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in ' 'bronchial transient secretory cells', 'volume': '39', 'author': 'Lukassen', 'year': '2020', 'journal-title': 'EMBO J.'}, { 'key': 'ref_79', 'doi-asserted-by': 'crossref', 'first-page': '110271', 'DOI': '10.1016/j.mehy.2020.110271', 'article-title': 'Relevance of SARS-CoV-2 related factors ACE2 and TMPRSS2 expressions in ' 'gastrointestinal tissue with pathogenesis of digestive symptoms, ' 'diabetes-associated mortality, and disease recurrence in COVID-19 ' 'patients', 'volume': '144', 'author': 'Kumar', 'year': '2020', 'journal-title': 'Med. Hypotheses'}, { 'key': 'ref_80', 'doi-asserted-by': 'crossref', 'first-page': '190', 'DOI': '10.1016/j.jtos.2020.05.013', 'article-title': 'Co-expression of SARS-CoV-2 entry genes in the superficial adult human ' 'conjunctival, limbal and corneal epithelium suggests an additional ' 'route of entry via the ocular surface', 'volume': '19', 'author': 'Collin', 'year': '2021', 'journal-title': 'Ocul. Surf.'}, { 'key': 'ref_81', 'doi-asserted-by': 'crossref', 'first-page': '185', 'DOI': '10.1007/s11684-020-0754-0', 'article-title': 'Single-cell RNA-seq data analysis on the receptor ACE2 expression ' 'reveals the potential risk of different human organs vulnerable to ' '2019-nCoV infection', 'volume': '14', 'author': 'Zou', 'year': '2020', 'journal-title': 'Front. Med.'}, { 'key': 'ref_82', 'doi-asserted-by': 'crossref', 'first-page': '134', 'DOI': '10.1002/1096-9896(2000)9999:9999<::AID-PATH743>3.0.CO;2-T', 'article-title': 'Expression of transmembrane serine protease TMPRSS2 in mouse and human ' 'tissues', 'volume': '193', 'author': 'Vaarala', 'year': '2001', 'journal-title': 'J. Pathol.'}, { 'key': 'ref_83', 'doi-asserted-by': 'crossref', 'first-page': '525', 'DOI': '10.1016/j.physbeh.2010.03.018', 'article-title': 'The renin angiotensin system and the metabolic syndrome', 'volume': '100', 'author': 'Krause', 'year': '2010', 'journal-title': 'Physiol. Behav.'}, { 'key': 'ref_84', 'doi-asserted-by': 'crossref', 'first-page': '317', 'DOI': '10.3389/fcimb.2020.00317', 'article-title': 'ACE2, much more than just a receptor for SARS-COV-2', 'volume': '10', 'author': 'Samavati', 'year': '2020', 'journal-title': 'Front. Cell Infect. Microbiol.'}, { 'key': 'ref_85', 'doi-asserted-by': 'crossref', 'first-page': '7635', 'DOI': '10.1038/s41598-020-64368-8', 'article-title': 'Inhibition of Influenza A virus propagation by benzoselenoxanthenes ' 'stabilizing TMPRSS2 Gene G-quadruplex and hence down-regulating TMPRSS2 ' 'expression', 'volume': '10', 'author': 'Shen', 'year': '2020', 'journal-title': 'Sci. Rep.'}, { 'key': 'ref_86', 'doi-asserted-by': 'crossref', 'first-page': '437', 'DOI': '10.1002/hep.27426', 'article-title': 'Transmembrane serine protease TMPRSS2 activates hepatitis C virus ' 'infection', 'volume': '61', 'author': 'Esumi', 'year': '2015', 'journal-title': 'Hepatology'}, { 'key': 'ref_87', 'doi-asserted-by': 'crossref', 'first-page': '12552', 'DOI': '10.1128/JVI.01890-13', 'article-title': 'Middle East respiratory syndrome coronavirus infection mediated by the ' 'transmembrane serine protease TMPRSS2', 'volume': '87', 'author': 'Shirato', 'year': '2013', 'journal-title': 'J. Virol.'}, { 'key': 'ref_88', 'doi-asserted-by': 'crossref', 'first-page': '5502', 'DOI': '10.1128/JVI.00128-13', 'article-title': 'The spike protein of the emerging betacoronavirus EMC uses a novel ' 'coronavirus receptor for entry, can be activated by TMPRSS2, and is ' 'targeted by neutralizing antibodies', 'volume': '87', 'author': 'Gierer', 'year': '2013', 'journal-title': 'J. Virol.'}, { 'key': 'ref_89', 'doi-asserted-by': 'crossref', 'first-page': 'e00649-19', 'DOI': '10.1128/JVI.00649-19', 'article-title': 'TMPRSS2 is the major activating protease of influenza A virus in ' 'primary human airway cells and influenza B virus in human type II ' 'pneumocytes', 'volume': '93', 'author': 'Limburg', 'year': '2019', 'journal-title': 'J. Virol.'}, { 'key': 'ref_90', 'doi-asserted-by': 'crossref', 'first-page': 'e01815-18', 'DOI': '10.1128/JVI.01815-18', 'article-title': 'TMPRSS2 contributes to virus spread and immunopathology in the airways ' 'of murine models after coronavirus infection', 'volume': '93', 'author': 'Okamura', 'year': '2019', 'journal-title': 'J. Virol.'}, { 'key': 'ref_91', 'doi-asserted-by': 'crossref', 'first-page': 'e13168', 'DOI': '10.1111/acel.13168', 'article-title': 'Individual variation of the SARS-CoV-2 receptor ACE2 gene expression ' 'and regulation', 'volume': '19', 'author': 'Chen', 'year': '2020', 'journal-title': 'Aging Cell'}, { 'key': 'ref_92', 'doi-asserted-by': 'crossref', 'first-page': '104621', 'DOI': '10.1016/j.micpath.2020.104621', 'article-title': 'ACE2 and TMPRSS2 polymorphisms in various diseases with special ' 'reference to its impact on COVID-19 disease', 'volume': '150', 'author': 'Singh', 'year': '2021', 'journal-title': 'Microb. Pathog.'}, { 'key': 'ref_93', 'doi-asserted-by': 'crossref', 'first-page': '143', 'DOI': '10.1016/j.biochi.2020.11.004', 'article-title': 'Molecular docking simulation reveals ACE2 polymorphisms that may ' 'increase the affinity of ACE2 with the SARS-CoV-2 spike protein', 'volume': '180', 'author': 'Calcagnile', 'year': '2021', 'journal-title': 'Biochimie'}, { 'key': 'ref_94', 'doi-asserted-by': 'crossref', 'first-page': '263', 'DOI': '10.1016/j.bbrc.2020.05.179', 'article-title': 'Genetic variants that influence SARS-CoV-2 receptor TMPRSS2 expression ' 'among population cohorts from multiple continents', 'volume': '529', 'author': 'Irham', 'year': '2020', 'journal-title': 'Biochem. Biophys. Res. Commun.'}, { 'key': 'ref_95', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1016/j.omtm.2020.05.013', 'article-title': 'Airways expression of SARS-CoV-2 receptor, ACE2, and TMPRSS2 is lower ' 'in children than adults and increases with smoking and COPD', 'volume': '18', 'author': 'Alabed', 'year': '2020', 'journal-title': 'Mol. Ther. Methods Clin. Dev.'}, { 'key': 'ref_96', 'doi-asserted-by': 'crossref', 'first-page': 'e62522', 'DOI': '10.7554/eLife.62522', 'article-title': 'Single-cell multiomic profiling of human lungs reveals ' 'cell-type-specific and age-dynamic control of SARS-CoV-2 host genes', 'volume': '9', 'author': 'Wang', 'year': '2020', 'journal-title': 'Elife'}, { 'key': 'ref_97', 'doi-asserted-by': 'crossref', 'first-page': '4684', 'DOI': '10.1016/j.csbj.2021.08.029', 'article-title': 'Co-crystallization and structure determination: An effective direction ' 'for anti-SARS-CoV-2 drug discovery', 'volume': '19', 'author': 'Wang', 'year': '2021', 'journal-title': 'Comput. Struct. Biotechnol. J.'}, { 'key': 'ref_98', 'doi-asserted-by': 'crossref', 'unstructured': 'Mackin, R.T., Edwards, J.V., Atuk, E.B., Beltrami, N., Condon, B.D., ' 'Jayawickramarajah, J., and French, A.D. (2022). Structure/function ' 'analysis of truncated amino-terminal ACE2 peptide analogs that bind to ' 'SARS-CoV-2 spike glycoprotein. Molecules, 27.', 'DOI': '10.3390/molecules27072070'}, { 'key': 'ref_99', 'doi-asserted-by': 'crossref', 'first-page': 'e13426', 'DOI': '10.15252/emmm.202013426', 'article-title': 'Human soluble ACE2 improves the effect of remdesivir in SARS-CoV-2 ' 'infection', 'volume': '13', 'author': 'Monteil', 'year': '2021', 'journal-title': 'EMBO Mol. Med.'}, { 'key': 'ref_100', 'doi-asserted-by': 'crossref', 'first-page': '416', 'DOI': '10.1165/rcmb.2020-0322PS', 'article-title': 'Targeting ACE2 for COVID-19 Therapy: Opportunities and challenges', 'volume': '64', 'author': 'Jia', 'year': '2021', 'journal-title': 'Am. J. Respir. Cell Mol. Biol.'}, { 'key': 'ref_101', 'doi-asserted-by': 'crossref', 'first-page': '36', 'DOI': '10.1016/j.metabol.2019.03.006', 'article-title': 'Angiotensin-(1-7), adipokines and inflammation', 'volume': '95', 'author': 'Lelis', 'year': '2019', 'journal-title': 'Metabolism'}, { 'key': 'ref_102', 'doi-asserted-by': 'crossref', 'first-page': '586', 'DOI': '10.1007/s00134-020-05985-9', 'article-title': 'Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: ' 'Molecular mechanisms and potential therapeutic target', 'volume': '46', 'author': 'Zhang', 'year': '2020', 'journal-title': 'Intensive Care Med.'}, { 'key': 'ref_103', 'doi-asserted-by': 'crossref', 'first-page': '59', 'DOI': '10.1016/j.bbi.2020.04.046', 'article-title': 'Current status of potential therapeutic candidates for the COVID-19 ' 'crisis', 'volume': '87', 'author': 'Zhang', 'year': '2020', 'journal-title': 'Brain Behav. Immun.'}, { 'key': 'ref_104', 'doi-asserted-by': 'crossref', 'first-page': '965', 'DOI': '10.1128/MCB.26.3.965-975.2006', 'article-title': 'Phenotypic analysis of mice lacking the TMPRSS2-encoded protease', 'volume': '26', 'author': 'Kim', 'year': '2006', 'journal-title': 'Mol. Cell Biol.'}, { 'key': 'ref_105', 'doi-asserted-by': 'crossref', 'first-page': '779', 'DOI': '10.1158/2159-8290.CD-20-0451', 'article-title': 'TMPRSS2 and COVID-19: Serendipity or opportunity for intervention?', 'volume': '10', 'author': 'Stopsack', 'year': '2020', 'journal-title': 'Cancer Discov.'}, { 'key': 'ref_106', 'doi-asserted-by': 'crossref', 'first-page': 'e202000786', 'DOI': '10.26508/lsa.202000786', 'article-title': 'TMPRSS2 and furin are both essential for proteolytic activation of ' 'SARS-CoV-2 in human airway cells', 'volume': '3', 'author': 'Bestle', 'year': '2020', 'journal-title': 'Life Sci. Alliance'}, { 'key': 'ref_107', 'doi-asserted-by': 'crossref', 'first-page': '100849', 'DOI': '10.1016/j.eclinm.2021.100849', 'article-title': 'Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients ' 'hospitalized with COVID-19- A double-blind randomized controlled trial', 'volume': '35', 'author': 'Gunst', 'year': '2021', 'journal-title': 'EClinicalMedicine'}, { 'key': 'ref_108', 'doi-asserted-by': 'crossref', 'first-page': '340', 'DOI': '10.1038/s41586-022-04661-w', 'article-title': 'A TMPRSS2 inhibitor acts as a pan-SARS-CoV-2 prophylactic and ' 'therapeutic', 'volume': '605', 'author': 'Shapira', 'year': '2022', 'journal-title': 'Nature'}, { 'key': 'ref_109', 'doi-asserted-by': 'crossref', 'first-page': 'e2108728118', 'DOI': '10.1073/pnas.2108728118', 'article-title': 'A novel class of TMPRSS2 inhibitors potently block SARS-CoV-2 and ' 'MERS-CoV viral entry and protect human epithelial lung cells', 'volume': '118', 'author': 'Mahoney', 'year': '2021', 'journal-title': 'Proc. Natl. Acad. Sci. USA'}, { 'key': 'ref_110', 'doi-asserted-by': 'crossref', 'unstructured': 'Rahman, N., Basharat, Z., Yousuf, M., Castaldo, G., Rastrelli, L., and ' 'Khan, H. (2020). Virtual screening of natural products against Type II ' 'transmembrane serine protease (TMPRSS2), the priming agent of ' 'coronavirus 2 (SARS-CoV-2). Molecules, 25.', 'DOI': '10.3390/molecules25102271'}, { 'key': 'ref_111', 'doi-asserted-by': 'crossref', 'first-page': '725528', 'DOI': '10.3389/fmolb.2021.725528', 'article-title': 'Host serine proteases: A potential targeted therapy for COVID-19 and ' 'influenza', 'volume': '8', 'author': 'Ardalan', 'year': '2021', 'journal-title': 'Front. Mol. Biosci.'}, { 'key': 'ref_112', 'doi-asserted-by': 'crossref', 'first-page': '1124', 'DOI': '10.1021/acsptsci.0c00221', 'article-title': 'Discovery of TMPRSS2 inhibitors from virtual screening as a potential ' 'treatment of COVID-19', 'volume': '4', 'author': 'Hu', 'year': '2021', 'journal-title': 'ACS Pharmacol. Transl. Sci.'}, { 'key': 'ref_113', 'doi-asserted-by': 'crossref', 'first-page': '100870', 'DOI': '10.1016/j.imu.2022.100870', 'article-title': 'Discovery of novel TMPRSS2 inhibitors for COVID-19 using in silico ' 'fragment-based drug design, molecular docking, molecular dynamics, and ' 'quantum mechanics studies', 'volume': '29', 'author': 'Alzain', 'year': '2022', 'journal-title': 'Inform. Med. Unlocked'}, { 'key': 'ref_114', 'doi-asserted-by': 'crossref', 'unstructured': 'Mahgoub, M.A., Alnaem, A., Fadlelmola, M., Abo-Idris, M., Makki, A.A., ' 'Abdelgadir, A.A., and Alzain, A.A. (2022). Discovery of novel potential ' 'inhibitors of TMPRSS2 and Mpro of SARS-CoV-2 using E-pharmacophore and ' 'docking-based virtual screening combined with molecular dynamic and ' 'quantum mechanics. J. Biomol. Struct. Dyn., 1–14.', 'DOI': '10.1080/07391102.2022.2112080'}, { 'key': 'ref_115', 'doi-asserted-by': 'crossref', 'first-page': '1609', 'DOI': '10.1007/s11224-022-01991-3', 'article-title': 'Identification, virtual screening and molecular dynamic analysis of ' 'novel TMPRSS2 inhibitors from natural compound database as potential ' 'entry-blocking agents in SARS-CoV-2 therapy', 'volume': '33', 'author': 'Manandhar', 'year': '2022', 'journal-title': 'Struct. Chem.'}, { 'key': 'ref_116', 'doi-asserted-by': 'crossref', 'first-page': 'e0284', 'DOI': '10.1097/CCE.0000000000000284', 'article-title': 'Camostat mesylate may reduce severity of coronavirus disease 2019 ' 'sepsis: A first observation', 'volume': '2', 'author': 'Moerer', 'year': '2020', 'journal-title': 'Crit. Care Explor.'}, { 'key': 'ref_117', 'doi-asserted-by': 'crossref', 'first-page': '392', 'DOI': '10.1186/s13054-020-03078-z', 'article-title': 'Nafamostat mesylate treatment in combination with favipiravir for ' 'patients critically ill with COVID-19: A case series', 'volume': '24', 'author': 'Doi', 'year': '2020', 'journal-title': 'Crit. Care'}, { 'key': 'ref_118', 'doi-asserted-by': 'crossref', 'first-page': '500', 'DOI': '10.1016/j.ijid.2020.05.072', 'article-title': 'Three cases of treatment with nafamostat in elderly patients with ' 'COVID-19 pneumonia who need oxygen therapy', 'volume': '96', 'author': 'Jang', 'year': '2020', 'journal-title': 'Int. J. Infect. Dis.'}, { 'key': 'ref_119', 'doi-asserted-by': 'crossref', 'first-page': '1161', 'DOI': '10.1038/s41564-022-01143-7', 'article-title': 'SARS-CoV-2 Omicron is an immune escape variant with an altered cell ' 'entry pathway', 'volume': '7', 'author': 'Willett', 'year': '2022', 'journal-title': 'Nat. Microbiol.'}, { 'key': 'ref_120', 'doi-asserted-by': 'crossref', 'first-page': '144', 'DOI': '10.1038/s41577-022-00681-9', 'article-title': 'Omicron entry route', 'volume': '22', 'author': 'Pia', 'year': '2022', 'journal-title': 'Nat. Rev. Immunol.'}, { 'key': 'ref_121', 'doi-asserted-by': 'crossref', 'unstructured': 'Peacock, T.P., Brown, J.C., Zhou, J., Thakur, N., Sukhova, K., Newman, ' 'J., Kugathasan, R., Yan, A.W.C., Furnon, W., and Lorenzo, G.D. (2021). ' 'The altered entry pathway and antigenic distance of the SARS-CoV-2 ' 'Omicron variant map to separate domains of spike protein. bioRxiv.', 'DOI': '10.1101/2021.12.31.474653'}, { 'key': 'ref_122', 'doi-asserted-by': 'crossref', 'first-page': '649', 'DOI': '10.1038/s41443-021-00524-6', 'article-title': 'Androgens and COVID-19: Exploring the role of testosterone replacement ' 'therapy', 'volume': '34', 'author': 'Punjani', 'year': '2022', 'journal-title': 'Int. J. Impot. Res.'}, { 'key': 'ref_123', 'first-page': '45', 'article-title': 'The role of androgen receptor mutations in progression of prostate ' 'cancer', 'volume': 'Volume 1', 'author': 'Neri', 'year': '2013', 'journal-title': 'Advances in Genome Science, Changing Views on Living Organisms'}, { 'key': 'ref_124', 'doi-asserted-by': 'crossref', 'first-page': '18', 'DOI': '10.2174/138920209787581307', 'article-title': 'The role of androgen receptor mutations in prostate cancer progression', 'volume': '10', 'author': 'Brooke', 'year': '2009', 'journal-title': 'Current Genom.'}, { 'key': 'ref_125', 'doi-asserted-by': 'crossref', 'first-page': '594', 'DOI': '10.3389/fendo.2018.00594', 'article-title': 'The divergent function of androgen receptor in breast cancer; analysis ' 'of steroid mediators and tumor intracrinology', 'volume': '9', 'author': 'Bleach', 'year': '2018', 'journal-title': 'Front. Endocrinol.'}, { 'key': 'ref_126', 'doi-asserted-by': 'crossref', 'first-page': '858', 'DOI': '10.3389/fonc.2019.00858', 'article-title': 'Androgen receptor signaling in the development of castration-resistant ' 'prostate cancer', 'volume': '9', 'author': 'Feng', 'year': '2019', 'journal-title': 'Front. Oncol.'}, { 'key': 'ref_127', 'doi-asserted-by': 'crossref', 'unstructured': 'Dart, D.A., Waxman, J., Aboagye, E.O., and Bevan, C.L. (2013). ' 'Visualising androgen receptor activity in male and female mice. PLoS ' 'ONE, 8.', 'DOI': '10.1371/journal.pone.0071694'}, { 'key': 'ref_128', 'doi-asserted-by': 'crossref', 'first-page': '14', 'DOI': '10.1016/j.mce.2009.12.022', 'article-title': 'Androgen receptor and androgen-dependent gene expression in lung', 'volume': '317', 'author': 'Mikkonen', 'year': '2010', 'journal-title': 'Mol. Cell Endocrinol.'}, { 'key': 'ref_129', 'doi-asserted-by': 'crossref', 'first-page': '11130', 'DOI': '10.1038/s41598-021-90491-1', 'article-title': 'Androgen regulation of pulmonary AR, TMPRSS2 and ACE2 with implications ' 'for sex-discordant COVID-19 outcomes', 'volume': '11', 'author': 'Baratchian', 'year': '2021', 'journal-title': 'Sci. Rep.'}, { 'key': 'ref_130', 'doi-asserted-by': 'crossref', 'first-page': '4068', 'DOI': '10.1038/s41467-021-24342-y', 'article-title': 'The antiandrogen enzalutamide downregulates TMPRSS2 and reduces ' 'cellular entry of SARS-CoV-2 in human lung cells', 'volume': '12', 'author': 'Leach', 'year': '2021', 'journal-title': 'Nat. Commun.'}, { 'key': 'ref_131', 'doi-asserted-by': 'crossref', 'first-page': 'bvac047', 'DOI': '10.1210/jendso/bvac047', 'article-title': 'Association Between Asthma and Reduced Androgen Receptor Expression in ' 'Airways', 'volume': '6', 'author': 'McManus', 'year': '2022', 'journal-title': 'J. Endocr. Soc.'}, { 'key': 'ref_132', 'doi-asserted-by': 'crossref', 'first-page': '1012', 'DOI': '10.1126/science.abb7314', 'article-title': 'Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman ' 'primate model', 'volume': '368', 'author': 'Rockx', 'year': '2020', 'journal-title': 'Science'}, { 'key': 'ref_133', 'doi-asserted-by': 'crossref', 'first-page': '2028', 'DOI': '10.1210/me.2013-1098', 'article-title': 'Androgen regulation of the TMPRSS2 gene and the effect of a SNP in an ' 'androgen response element', 'volume': '27', 'author': 'Clinckemalie', 'year': '2013', 'journal-title': 'Mol. Endocrinol.'}, { 'key': 'ref_134', 'doi-asserted-by': 'crossref', 'first-page': '866', 'DOI': '10.1038/s41467-021-21171-x', 'article-title': 'Distinct mechanisms for TMPRSS2 expression explain organ-specific ' 'inhibition of SARS-CoV-2 infection by enzalutamide', 'volume': '12', 'author': 'Li', 'year': '2021', 'journal-title': 'Nat. Commun.'}, { 'key': 'ref_135', 'unstructured': '(2022, November 01). Science. Wadman, M. Why Coronavirus Hits Men ' 'Harder: Sex Hormones Offer Clues. Available online: ' 'https://www.science.org/content/article/why-coronavirus-hits-men-harder-sex-hormones-offer-clues.'}, { 'key': 'ref_136', 'doi-asserted-by': 'crossref', 'first-page': 'bqab114', 'DOI': '10.1210/endocr/bqab114', 'article-title': 'Do anti-androgens have potential as therapeutics for COVID-19?', 'volume': '162', 'year': '2021', 'journal-title': 'Endocrinology'}, { 'key': 'ref_137', 'doi-asserted-by': 'crossref', 'first-page': '261', 'DOI': '10.1586/17469872.1.2.261', 'article-title': 'Antiandrogen therapy for androgenetic alopecia', 'volume': '1', 'author': 'Yip', 'year': '2014', 'journal-title': 'Expert Rev. Dermatol.'}, { 'key': 'ref_138', 'doi-asserted-by': 'crossref', 'first-page': 'S362', 'DOI': '10.21037/atm.2019.09.53', 'article-title': 'The importance of antiandrogen in prostate cancer treatment', 'volume': '7', 'author': 'Lanz', 'year': '2019', 'journal-title': 'Ann. Transl. Med.'}, { 'key': 'ref_139', 'doi-asserted-by': 'crossref', 'first-page': '1413', 'DOI': '10.1634/theoncologist.2011-0164', 'article-title': 'Revisiting the role of antiandrogen strategies in ovarian cancer', 'volume': '16', 'author': 'Dedes', 'year': '2011', 'journal-title': 'Oncologist'}, { 'key': 'ref_140', 'doi-asserted-by': 'crossref', 'first-page': 'R257', 'DOI': '10.1530/JME-14-0030', 'article-title': 'Revising the role of the androgen receptor in breast cancer', 'volume': '52', 'author': 'Fioretti', 'year': '2014', 'journal-title': 'J. Mol. Endocrinol.'}, { 'key': 'ref_141', 'doi-asserted-by': 'crossref', 'unstructured': 'Anestis, A., Zoi, I., Papavassiliou, A.G., and Karamouzis, M.V. (2020). ' 'Androgen receptor in breast cancer-clinical and preclinical research ' 'insights. Molecules, 25.', 'DOI': '10.3390/molecules25020358'}, { 'key': 'ref_142', 'doi-asserted-by': 'crossref', 'first-page': '91', 'DOI': '10.1586/eem.11.85', 'article-title': 'Androgens and polycystic ovary syndrome', 'volume': '7', 'author': 'Alpanes', 'year': '2012', 'journal-title': 'Expert Rev. Endocrinol. Metab.'}, { 'key': 'ref_143', 'doi-asserted-by': 'crossref', 'first-page': '102254', 'DOI': '10.1016/j.isci.2021.102254', 'article-title': 'Targeting androgen regulation of TMPRSS2 and ACE2 as a therapeutic ' 'strategy to combat COVID-19', 'volume': '24', 'author': 'Deng', 'year': '2021', 'journal-title': 'iScience'}, { 'key': 'ref_144', 'doi-asserted-by': 'crossref', 'first-page': '1040', 'DOI': '10.1016/j.annonc.2020.04.479', 'article-title': 'Androgen-deprivation therapies for prostate cancer and risk of ' 'infection by SARS-CoV-2: A population-based study (N = 4532)', 'volume': '31', 'author': 'Montopoli', 'year': '2020', 'journal-title': 'Ann. Oncol.'}, { 'key': 'ref_145', 'doi-asserted-by': 'crossref', 'first-page': '1419', 'DOI': '10.1016/j.annonc.2020.06.023', 'article-title': 'Does androgen deprivation therapy protect against severe complications ' 'from COVID-19?', 'volume': '31', 'author': 'Patel', 'year': '2020', 'journal-title': 'Ann. Oncol.'}, { 'key': 'ref_146', 'doi-asserted-by': 'crossref', 'first-page': '774773', 'DOI': '10.3389/fmed.2022.774773', 'article-title': 'A population-level analysis of the protective effects of androgen ' 'deprivation therapy against COVID-19 disease incidence and severity', 'volume': '9', 'author': 'Lee', 'year': '2022', 'journal-title': 'Front. Med.'}, { 'key': 'ref_147', 'doi-asserted-by': 'crossref', 'first-page': 'e243', 'DOI': '10.1111/jdv.17021', 'article-title': '5-alpha-reductase inhibitors are associated with reduced frequency of ' 'COVID-19 symptoms in males with androgenetic alopecia', 'volume': '35', 'author': 'McCoy', 'year': '2021', 'journal-title': 'J. Eur. Acad. Dermatol. Venereol.'}, { 'key': 'ref_148', 'doi-asserted-by': 'crossref', 'first-page': '285', 'DOI': '10.1016/j.eururo.2021.12.013', 'article-title': 'A Phase 2 Trial of the effect of antiandrogen therapy on COVID-19 ' 'outcome: No evidence of benefit, supported by epidemiology and in vitro ' 'data', 'volume': '81', 'author': 'Welen', 'year': '2022', 'journal-title': 'Eur. Urol.'}, { 'key': 'ref_149', 'doi-asserted-by': 'crossref', 'first-page': 'e227852', 'DOI': '10.1001/jamanetworkopen.2022.7852', 'article-title': 'Effect of androgen suppression on clinical outcomes in hospitalized men ' 'with COVID-19: The HITCH randomized clinical trial', 'volume': '5', 'author': 'Nickols', 'year': '2022', 'journal-title': 'JAMA Netw. Open'}, { 'key': 'ref_150', 'doi-asserted-by': 'crossref', 'first-page': '2905', 'DOI': '10.1021/jacs.1c08402', 'article-title': 'Ultralarge virtual screening identifies SARS-CoV-2 main protease ' 'inhibitors with broad-spectrum activity against coronaviruses', 'volume': '144', 'author': 'Luttens', 'year': '2022', 'journal-title': 'J. Am. Chem. Soc.'}, { 'key': 'ref_151', 'doi-asserted-by': 'crossref', 'first-page': '1373', 'DOI': '10.1002/jmv.27517', 'article-title': 'Broad-spectrum prodrugs with anti-SARS-CoV-2 activities: Strategies, ' 'benefits, and challenges', 'volume': '94', 'author': 'Wang', 'year': '2022', 'journal-title': 'J. Med. Virol.'}], 'container-title': 'Viruses', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.mdpi.com/1999-4915/14/12/2728/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 12, 7]], 'date-time': '2022-12-07T07:57:49Z', 'timestamp': 1670399869000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.mdpi.com/1999-4915/14/12/2728'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 12, 7]]}, 'references-count': 151, 'journal-issue': {'issue': '12', 'published-online': {'date-parts': [[2022, 12]]}}, 'alternative-id': ['v14122728'], 'URL': 'http://dx.doi.org/10.3390/v14122728', 'relation': { 'has-preprint': [ { 'id-type': 'doi', 'id': '10.20944/preprints202211.0075.v1', 'asserted-by': 'object'}]}, 'ISSN': ['1999-4915'], 'subject': [], 'container-title-short': 'Viruses', 'published': {'date-parts': [[2022, 12, 7]]}}
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. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment 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