Abstract The COVID ‐19 pandemic caused by SARS ‐CoV‐2 has is a global health challenge. Angiotensin‐converting enzyme 2 ( ACE 2 ) is the host receptor for SARS ‐CoV‐2 entry. Recent studies have suggested that patients with hypertension and diabetes treated with ACE inhibitors ( ACEI s) or angiotensin receptor blockers have a higher risk of COVID ‐19 infection as these drugs could upregulate ACE 2 , motivating the study of ACE 2 modulation by drugs in current clinical use. Here, we mined published datasets to determine the effects of hundreds of clinically approved drugs on ACE 2 expression. We find that ACEI s are enriched for ACE 2 ‐upregulating drugs, while antineoplastic agents are enriched for ACE 2 ‐downregulating drugs. Vorinostat and isotretinoin are the top ACE 2 up/downregulators, respectively, in cell lines. Dexamethasone, a corticosteroid used in treating severe acute respiratory syndrome and COVID ‐19, significantly upregulates ACE 2 both in vitro and in vivo . Further top ACE 2 regulators in vivo or 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 studying ACE 2 expression modulators. Analyzing large‐scale in vitro and in vivo publicly available transcriptomic data of drug treatments, we identify the effects of hundreds of clinically approved drugs on expression of ACE 2 , the host receptor of SARS ‐CoV‐2.
【저자키워드】 Dexamethasone, severe acute respiratory syndrome coronavirus 2, Coronavirus disease 2019, Chemical biology, Microbiology, Virology & Host Pathogen Interaction, angiotensin I‐converting enzyme 2, drug‐modifying