Ogunjinmi, Oluwadamilola D and Abdullahi, Tukur and Somji, Riaz-Ali and Bevan, Charlotte L and Barclay, Wendy S and Temperton, Nigel and Brooke, Greg N and Giotis, Efstathios (2024) The antiviral potential of the antiandrogen enzalutamide and the viral-androgen signaling interplay in seasonal coronaviruses. Journal of Medical Virology, 96 (3). e29540-. DOI https://doi.org/10.1002/jmv.29540
Ogunjinmi, Oluwadamilola D and Abdullahi, Tukur and Somji, Riaz-Ali and Bevan, Charlotte L and Barclay, Wendy S and Temperton, Nigel and Brooke, Greg N and Giotis, Efstathios (2024) The antiviral potential of the antiandrogen enzalutamide and the viral-androgen signaling interplay in seasonal coronaviruses. Journal of Medical Virology, 96 (3). e29540-. DOI https://doi.org/10.1002/jmv.29540
Ogunjinmi, Oluwadamilola D and Abdullahi, Tukur and Somji, Riaz-Ali and Bevan, Charlotte L and Barclay, Wendy S and Temperton, Nigel and Brooke, Greg N and Giotis, Efstathios (2024) The antiviral potential of the antiandrogen enzalutamide and the viral-androgen signaling interplay in seasonal coronaviruses. Journal of Medical Virology, 96 (3). e29540-. DOI https://doi.org/10.1002/jmv.29540
Abstract
The sex disparity in COVID-19 outcomes with males generally faring worse than females has been associated with the androgen-regulated expression of the protease TMPRSS2 and the cell receptor ACE2 in the lung and fueled interest in antiandrogens as potential antivirals. In this study, we explored enzalutamide, an antiandrogen used commonly to treat prostate cancer, as a potential antiviral against the human coronaviruses which cause seasonal respiratory infections (HCoV-NL63, −229E, and -OC43). Using lentivirus-pseudotyped and authentic HCoV, we report that enzalutamide reduced 229E and NL63 entry and infection in both TMPRSS2- and nonexpressing immortalized cells, suggesting a TMPRSS2-independent mechanism. However, no effect was observed against OC43. To decipher this distinction, we performed RNA-sequencing analysis on 229E- and OC43-infected primary human airway cells. Our results show a significant induction of androgen-responsive genes by 229E compared to OC43 at 24 and 72 h postinfection. The virus-mediated effect on AR-signaling was further confirmed with a consensus androgen response element-driven luciferase assay in androgen-depleted MRC-5 cells. Specifically, 229E induced luciferase-reporter activity in the presence and absence of the synthetic androgen mibolerone, while OC43 inhibited induction. These findings highlight a complex interplay between viral infections and androgen-signaling, offering insights for disparities in viral outcomes and antiviral interventions.
Item Type: | Article |
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Uncontrolled Keywords: | androgen response element; antiandrogens; enzalutamide; SARS-CoV-2; seasonal coronaviruses; TMPRSS2 |
Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 23 Aug 2024 16:17 |
Last Modified: | 23 Aug 2024 16:17 |
URI: | http://repository.essex.ac.uk/id/eprint/39036 |
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