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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/4241| Transcriptional Inhibition of Host Viral Entry Proteins as a Therapeutic Strategy for SARS-CoV-2 | |
| Wang Xinchen. Dhindsa Ryan. Povysil Gundula. Zoghbi Anthony. Motelow Joshua. Hostyk Joseph. Goldstein David. | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| 10.20944/preprints202003.0360.v1 | |
| There is an urgent need to identify effective therapies for COVID-19 given that a broadly available and effective vaccine is likely at least one year away. Here, we identify compounds that transcriptionally inhibit host proteins required for SARS-CoV-2 entry and should be evaluated for efficacy in SARS-CoV-2 viral infection assays. Recognizing the need for immediately available treatment options, we focused particular attention on FDA-approved drugs that could be immediately repurposed to treat COVID-19 patients. By mining publicly available gene expression data, we identify several compounds that down-regulate TMPRSS2, a protein required for SARS-CoV-2 entry that has emerged as a promising therapeutic target. Among these, we find twenty independent studies that implicate estrogen-related and androgen-related compounds as transcriptional modulators of TMPRSS2 expression, suggesting that these drugs and others acting on the pathway may be promising therapeutic candidates for COVID-19 for further testing. It is also noteworthy that TMPRSS2 has highly variable and skewed expression in humans, spanning two orders of magnitude with a small minority of individuals having extremely high expression. Combined with literature showing that TMPRSS2 loss-of-function in mouse is protective against SARS while anti-estrogen treatment predicted to increase TMPRSS2 expression exacerbates SARS, this observation raises the hypothesis that TMPRSS2 expression may positively correlate with severity in COVID-19. | |
| www.preprints.org | |
| 2020 | |
| Artículo | |
| https://www.preprints.org/manuscript/202003.0360/v1/download | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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| 1106123.pdf | 2.4 MB | Adobe PDF | Visualizar/Abrir |