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

doi:10.3390/biomedicines9040437

Biomedicines (Apr 2021)

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

Affiliations

Dean Gilham: Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada
Audrey L. Smith: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 NE Med Center, BCC 4.12.396, Omaha, NE 68198, USA
Li Fu: Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada
Dalia Y. Moore: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 NE Med Center, BCC 4.12.396, Omaha, NE 68198, USA
Abenaya Muralidharan: Department of Pathology and Microbiology, University of Nebraska Medical Center, 985900 Nebraska Medical Center, Omaha, NE 68198, USA
St. Patrick M. Reid: Department of Pathology and Microbiology, University of Nebraska Medical Center, 985900 Nebraska Medical Center, Omaha, NE 68198, USA
Stephanie C. Stotz: Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada
Jan O. Johansson: Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada
Michael Sweeney: Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada
Norman C. W. Wong: Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada
Ewelina Kulikowski: Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada
Dalia El-Gamal: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 NE Med Center, BCC 4.12.396, Omaha, NE 68198, USA

DOI: https://doi.org/10.3390/biomedicines9040437
Journal volume & issue: Vol. 9, no. 4
p. 437

Abstract

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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.

Published in Biomedicines

ISSN: 2227-9059 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/biomedicines

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