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

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...

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Autores principales: Gilham, Dean, Smith, Audrey L., Fu, Li, Moore, Dalia Y., Muralidharan, Abenaya, Reid, St. Patrick M., Stotz, Stephanie C., Johansson, Jan O., Sweeney, Michael, Wong, Norman C. W., Kulikowski, Ewelina, El-Gamal, Dalia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072876/
https://www.ncbi.nlm.nih.gov/pubmed/33919584
http://dx.doi.org/10.3390/biomedicines9040437
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author Gilham, Dean
Smith, Audrey L.
Fu, Li
Moore, Dalia Y.
Muralidharan, Abenaya
Reid, St. Patrick M.
Stotz, Stephanie C.
Johansson, Jan O.
Sweeney, Michael
Wong, Norman C. W.
Kulikowski, Ewelina
El-Gamal, Dalia
author_facet Gilham, Dean
Smith, Audrey L.
Fu, Li
Moore, Dalia Y.
Muralidharan, Abenaya
Reid, St. Patrick M.
Stotz, Stephanie C.
Johansson, Jan O.
Sweeney, Michael
Wong, Norman C. W.
Kulikowski, Ewelina
El-Gamal, Dalia
author_sort Gilham, Dean
collection PubMed
description 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.
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spelling pubmed-80728762021-04-27 Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro Gilham, Dean Smith, Audrey L. Fu, Li Moore, Dalia Y. Muralidharan, Abenaya Reid, St. Patrick M. Stotz, Stephanie C. Johansson, Jan O. Sweeney, Michael Wong, Norman C. W. Kulikowski, Ewelina El-Gamal, Dalia Biomedicines Article 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. MDPI 2021-04-18 /pmc/articles/PMC8072876/ /pubmed/33919584 http://dx.doi.org/10.3390/biomedicines9040437 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gilham, Dean
Smith, Audrey L.
Fu, Li
Moore, Dalia Y.
Muralidharan, Abenaya
Reid, St. Patrick M.
Stotz, Stephanie C.
Johansson, Jan O.
Sweeney, Michael
Wong, Norman C. W.
Kulikowski, Ewelina
El-Gamal, Dalia
Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro
title Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro
title_full Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro
title_fullStr Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro
title_full_unstemmed Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro
title_short Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro
title_sort bromodomain and extraterminal protein inhibitor, apabetalone (rvx-208), reduces ace2 expression and attenuates sars-cov-2 infection in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072876/
https://www.ncbi.nlm.nih.gov/pubmed/33919584
http://dx.doi.org/10.3390/biomedicines9040437
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