Open AccessIn vitro and in vivo identification of clinically approved drugs that modify ACE 2 expression
Author(s) -
Sinha Sanju,
Cheng Kuoyuan,
Schäffer Alejandro A,
Aldape Kenneth,
Schiff Eyal,
Ruppin Eytan
Publication year - 2020
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20209628
Subject(s) - biology , in vivo , in vitro , identification (biology) , computational biology , pharmacology , genetics , botany
The COVID ‐19 pandemic caused by SARS ‐CoV‐2 has been 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.