Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro.
BET proteins
COVID-19
SARS-CoV-2
angiotensin-converting enzyme 2 (ACE2)
apabetalone
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
18 Apr 2021
18 Apr 2021
Historique:
received:
22
03
2021
revised:
09
04
2021
accepted:
15
04
2021
entrez:
30
4
2021
pubmed:
1
5
2021
medline:
1
5
2021
Statut:
epublish
Résumé
Effective therapeutics are urgently needed to counter infection and improve outcomes for patients suffering from COVID-19 and to combat this pandemic. Manipulation of epigenetic machinery to influence viral infectivity of host cells is a relatively unexplored area. The bromodomain and extraterminal (BET) family of epigenetic readers have been reported to modulate SARS-CoV-2 infection. Herein, we demonstrate apabetalone, the most clinical advanced BET inhibitor, downregulates expression of cell surface receptors involved in SARS-CoV-2 entry, including angiotensin-converting enzyme 2 (ACE2) and dipeptidyl-peptidase 4 (DPP4 or CD26) in SARS-CoV-2 permissive cells. Moreover, we show that apabetalone inhibits SARS-CoV-2 infection in vitro to levels comparable to those of antiviral agents. Taken together, our study supports further evaluation of apabetalone to treat COVID-19, either alone or in combination with emerging therapeutics.
Identifiants
pubmed: 33919584
pii: biomedicines9040437
doi: 10.3390/biomedicines9040437
pmc: PMC8072876
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : College of Medicine, University of Nebraska Medical Center
ID : Covid rapid response grant
Organisme : University of Nebraska Medical Center
ID : start-up fund
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