Preprint Brief Report Version 1 This version is not peer-reviewed

Systematic Cell Line-Based Identification of Drugs Modifying ACE2 Expression

Version 1 : Received: 27 March 2020 / Approved: 31 March 2020 / Online: 31 March 2020 (05:08:29 CEST)

How to cite: Sinha, S.; Cheng, K.; Aldape, K.; Schiff, E.; Ruppin, E. Systematic Cell Line-Based Identification of Drugs Modifying ACE2 Expression. Preprints 2020, 2020030446 (doi: 10.20944/preprints202003.0446.v1). Sinha, S.; Cheng, K.; Aldape, K.; Schiff, E.; Ruppin, E. Systematic Cell Line-Based Identification of Drugs Modifying ACE2 Expression. Preprints 2020, 2020030446 (doi: 10.20944/preprints202003.0446.v1).

Abstract

The COVID-19 pandemic caused by SARS-COV-2 has infected over 500,000 people causing over 25,000 deaths in the last 10 weeks. A key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 (ACE2). Recent studies have reported that patients with hypertension and diabetes treated with ACE inhibitors or angiotensin receptor blockers might be at a higher risk of COVID-19 infection as these drugs have been reported to increase ACE2 expression. This has raised the need to systematically investigate the effect of different drugs including antihypertensives on modulating ACE2 expression. Here, we analyzed a publicly available CMAP dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules. We show that only one subclass of antihypertensives drugs - ACE inhibitors, are significantly enriched for drugs up-regulating ACE2 expression. Studying the effects of the 672 clinically approved drugs in CMAP, we chart the drug categories that affect ACE2 expression. Specifically, we find that panobinostat (an HDAC inhibitor) confers the highest up-regulation of ACE2 expression while isotretinoin (a vitamin A derivative) is its strongest down-regulator. Our results provide initial candidates guiding further in vitro and in vivo studies aimed at assessing drug effects on ACE2 expression.

Subject Areas

COVID19; infectious diseases

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