We present (preprint) an approach for identifying drug treatments modulating the expression of a key protein required for the SARS-CoV-2 virus entry – the ACE2 (angiotensin-converting enzyme 2) receptor. preprints.org/manuscript/202… 
Two weeks ago, Fang et al suggested that diabetes and hypertension patients treated with ACE-inhibitors & AR-blockers are at a higher risk for COVID-19 as these treatments may increase ACE2 expression.
This motivated us to ask this question – Which clinically approved drugs including antihypertensives may modulate ACE2 in lung tissue?
Mining and analyzing a large screen of in vitro drug treatment pre/post expression in cell lines (CMAP), we find that the ACE inhibitors are indeed the only subclass of antihypertensives drugs that are significantly enriched with drugs up-regulating ACE2 expression.
Next, studying the effects of all clinically approved drugs, we chart the drug categories that affect ACE2 expression.
On a drug level - panobinostat (an HDAC inhibitor) confers the highest up-regulation of ACE2 expression while isotretinoin (a vitamin A derivative) is its strongest down-regulator.
Studying in vivo treatment datasets from GEO, we find an overall signal corroborating our in vitro analysis.
More specifically, we find that dexamethasone, a corticosteroid widely used in severe acute respiratory syndrome (SARS) and also for treating COVID-19 patients, significantly up-regulates ACE2 both in vitro and in in vivo lung tissues.
In sum, our analysis provides candidate leads for guiding further in vitro and in vivo studies to assess the effects of specific drugs on ACE2 expression in the lung in a more focused and systematic manner.
