Bromodomain and extraterminal protein inhibitor, apabetalone (Rvx-208), reduces ace2 expression and attenuates sars-cov-2 infection in vitro

Dean Gilham, Audrey L. Smith, Li Fu, Dalia Y. Moore, Abenaya Muralidharan, St Patrick M. Reid, Stephanie C. Stotz, Jan O. Johansson, Michael Sweeney, Norman C.W. Wong, Ewelina Kulikowski, Dalia El-Gamal

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number437
JournalBiomedicines
Volume9
Issue number4
DOIs
StatePublished - Apr 2021

Keywords

  • Angiotensin-converting enzyme 2 (ACE2)
  • Apabetalone
  • BET proteins
  • COVID-19
  • SARS-CoV-2

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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