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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
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