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 combat this pandemic. Manipulation of epigenetic machinery influence viral infectivity host cells is a relatively unexplored area. The bromodomain extraterminal (BET) family readers have been reported modulate SARS-CoV-2 infection. Herein, we demonstrate apabetalone, the most clinical advanced BET inhibitor, downregulates expression cell surface receptors involved in entry, including angiotensin-converting enzyme 2 (ACE2) dipeptidyl-peptidase 4 (DPP4 or CD26) permissive cells. Moreover, show that apabetalone inhibits vitro levels comparable those antiviral agents. Taken together, our study supports further evaluation treat COVID-19, either alone combination with emerging therapeutics.