Version 1
: Received: 24 March 2020 / Approved: 24 March 2020 / Online: 24 March 2020 (14:26:57 CET)
Version 2
: Received: 27 April 2020 / Approved: 28 April 2020 / Online: 28 April 2020 (09:39:02 CEST)
How to cite:
Wang, X.; Dhindsa, R.; Povysil, G.; Zoghbi, A.; Motelow, J.; Hostyk, J.; Goldstein, D. Transcriptional Inhibition of Host Viral Entry Proteins as a Therapeutic Strategy for SARS-CoV-2. Preprints2020, 2020030360. https://doi.org/10.20944/preprints202003.0360.v1
Wang, X.; Dhindsa, R.; Povysil, G.; Zoghbi, A.; Motelow, J.; Hostyk, J.; Goldstein, D. Transcriptional Inhibition of Host Viral Entry Proteins as a Therapeutic Strategy for SARS-CoV-2. Preprints 2020, 2020030360. https://doi.org/10.20944/preprints202003.0360.v1
Wang, X.; Dhindsa, R.; Povysil, G.; Zoghbi, A.; Motelow, J.; Hostyk, J.; Goldstein, D. Transcriptional Inhibition of Host Viral Entry Proteins as a Therapeutic Strategy for SARS-CoV-2. Preprints2020, 2020030360. https://doi.org/10.20944/preprints202003.0360.v1
APA Style
Wang, X., Dhindsa, R., Povysil, G., Zoghbi, A., Motelow, J., Hostyk, J., & Goldstein, D. (2020). Transcriptional Inhibition of Host Viral Entry Proteins as a Therapeutic Strategy for SARS-CoV-2. Preprints. https://doi.org/10.20944/preprints202003.0360.v1
Chicago/Turabian Style
Wang, X., Joseph Hostyk and David Goldstein. 2020 "Transcriptional Inhibition of Host Viral Entry Proteins as a Therapeutic Strategy for SARS-CoV-2" Preprints. https://doi.org/10.20944/preprints202003.0360.v1
Abstract
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.
Keywords
SARS-CoV-2; transcriptional inhibition; COVID-19; drug repurposing; TMPRSS2
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
