In vitro and in vivo identification of clinically approved drugs that modify ACE2 expression.
Mol Syst Biol
; 16(7): e9628, 2020 07.
Article
in English
| MEDLINE | ID: covidwho-707164
ABSTRACT
The COVID-19 pandemic caused by SARS-CoV-2 has is a global health challenge. Angiotensin-converting enzyme 2 (ACE2) is the host receptor for SARS-CoV-2 entry. Recent studies have suggested that patients with hypertension and diabetes treated with ACE inhibitors (ACEIs) or angiotensin receptor blockers have a higher risk of COVID-19 infection as these drugs could upregulate ACE2, motivating the study of ACE2 modulation by drugs in current clinical use. Here, we mined published datasets to determine the effects of hundreds of clinically approved drugs on ACE2 expression. We find that ACEIs are enriched for ACE2-upregulating drugs, while antineoplastic agents are enriched for ACE2-downregulating drugs. Vorinostat and isotretinoin are the top ACE2 up/downregulators, respectively, in cell lines. Dexamethasone, a corticosteroid used in treating severe acute respiratory syndrome and COVID-19, significantly upregulates ACE2 both in vitro and in vivo. Further top ACE2 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 ACE2 expression modulators.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pneumonia, Viral
/
Angiotensin-Converting Enzyme Inhibitors
/
Coronavirus Infections
/
Angiotensin Receptor Antagonists
Type of study:
Prognostic study
Topics:
Traditional medicine
Limits:
Humans
Language:
English
Journal:
Mol Syst Biol
Journal subject:
Molecular Biology
/
Biotechnology
Year:
2020
Document Type:
Article
Affiliation country:
Msb.20209628
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