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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.
  • Gilham D; Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada.
  • Smith AL; 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.
  • Fu L; Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada.
  • Moore DY; 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.
  • Muralidharan A; Department of Pathology and Microbiology, University of Nebraska Medical Center, 985900 Nebraska Medical Center, Omaha, NE 68198, USA.
  • Reid SPM; Department of Pathology and Microbiology, University of Nebraska Medical Center, 985900 Nebraska Medical Center, Omaha, NE 68198, USA.
  • Stotz SC; Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada.
  • Johansson JO; Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada.
  • Sweeney M; Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada.
  • Wong NCW; Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada.
  • Kulikowski E; Resverlogix Corp., 300, 4820 Richard Road SW, Calgary, AB T3E 6L1, Canada.
  • El-Gamal D; 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.
Biomedicines ; 9(4)2021 Apr 18.
Article in English | MEDLINE | ID: covidwho-1194606
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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.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study Language: English Year: 2021 Document Type: Article Affiliation country: Biomedicines9040437

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study Language: English Year: 2021 Document Type: Article Affiliation country: Biomedicines9040437