In vitroandin vivoidentification of clinically approved drugs that modifyACE2expression

ABSTRACT

TheCOVID-19 pandemic caused bySARS-CoV-2 has is a global health challenge. Angiotensin-converting enzyme 2 (ACE2) is the host receptor forSARS-CoV-2 entry. Recent studies have suggested that patients with hypertension and diabetes treated withACEinhibitors (ACEIs) or angiotensin receptor blockers have a higher risk ofCOVID-19 infection as these drugs could upregulateACE2, motivating the study ofACE2modulation by drugs in current clinical use. Here, we mined published datasets to determine the effects of hundreds of clinically approved drugs onACE2expression. We find thatACEIs are enriched forACE2-upregulating drugs, while antineoplastic agents are enriched forACE2-downregulating drugs. Vorinostat and isotretinoin are the topACE2up/downregulators, respectively, in cell lines. Dexamethasone, a corticosteroid used in treating severe acute respiratory syndrome andCOVID-19, significantly upregulatesACE2bothin vitroandin vivo. Further topACE2regulatorsin vivoor in primary cells include erlotinib and bleomycin in the lung and vancomycin, cisplatin, and probenecid in the kidney. Our study provides leads for future work studyingACE2expression modulators.