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Article

Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro

1
Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada
2
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
3
Department of Pathology and Microbiology, University of Nebraska Medical Center, 985900 Nebraska Medical Center, Omaha, NE 68198, USA
*
Author to whom correspondence should be addressed.
Equal first author contribution.
The senior authors contributed equally.
Academic Editor: Jean A. Boutin
Biomedicines 2021, 9(4), 437; https://doi.org/10.3390/biomedicines9040437
Received: 22 March 2021 / Revised: 9 April 2021 / Accepted: 15 April 2021 / Published: 18 April 2021
(This article belongs to the Section Drug Discovery and Development)
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. View Full-Text
Keywords: COVID-19; SARS-CoV-2; BET proteins; apabetalone; angiotensin-converting enzyme 2 (ACE2) COVID-19; SARS-CoV-2; BET proteins; apabetalone; angiotensin-converting enzyme 2 (ACE2)
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MDPI and ACS Style

Gilham, D.; Smith, A.L.; Fu, L.; Moore, D.Y.; Muralidharan, A.; Reid, S.P.M.; Stotz, S.C.; Johansson, J.O.; Sweeney, M.; Wong, N.C.W.; Kulikowski, E.; El-Gamal, D. Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro. Biomedicines 2021, 9, 437. https://doi.org/10.3390/biomedicines9040437

AMA Style

Gilham D, Smith AL, Fu L, Moore DY, Muralidharan A, Reid SPM, Stotz SC, Johansson JO, Sweeney M, Wong NCW, Kulikowski E, El-Gamal D. Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro. Biomedicines. 2021; 9(4):437. https://doi.org/10.3390/biomedicines9040437

Chicago/Turabian Style

Gilham, Dean, Audrey L. Smith, Li Fu, Dalia Y. Moore, Abenaya Muralidharan, St. P.M. Reid, Stephanie C. Stotz, Jan O. Johansson, Michael Sweeney, Norman C.W. Wong, Ewelina Kulikowski, and Dalia El-Gamal. 2021. "Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro" Biomedicines 9, no. 4: 437. https://doi.org/10.3390/biomedicines9040437

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