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 CW Wong; Ewelina Kulikowski; Dalia El-Gamal

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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 CW Wong; Ewelina Kulikowski; Dalia El-Gamal.

Affiliation

Dean Gilham; Resverlogix Corp., Calgary, AB. Canada
Audrey L Smith; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
Li Fu; Resverlogix Corp., Calgar, AB, Canada
Dalia Y Moore; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
Abenaya Muralidharan; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
St. Patrick M Reid; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
Stephanie C Stotz; Resverlogix Corp., Calgary, AB, Canada
Jan O Johansson; Resverlogix Corp., Calgary, AB, Canada
Michael Sweeney; Resverlogix Corp., Calgary, AB, Canada
Norman CW Wong; Resverlogix Corp., Calgary, AB, Canada
Ewelina Kulikowski; Resverlogix Corp., Calgary, AB, Canada
Dalia El-Gamal; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA

Preprint in English | bioRxiv | ID: ppbiorxiv-432949

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ABSTRACT

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 antiviral agents. Taken together, our study supports further evaluation of apabetalone to treat COVID-19, either alone or in combination with emerging therapeutics. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=192 SRC="FIGDIR/small/432949v1_ufig1.gif" ALT="Figure 1"> View larger version (54K) org.highwire.dtl.DTLVardef@127e6c4org.highwire.dtl.DTLVardef@9f6d3aorg.highwire.dtl.DTLVardef@bbfe3borg.highwire.dtl.DTLVardef@2ffad8_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies / Prognostic study Language: English Year: 2021 Document type: Preprint

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Full text: Available Collection: Preprints Database: bioRxiv Type of study: Experimental_studies / Prognostic study Language: English Year: 2021 Document type: Preprint