Bromodomain Inhibition Blocks Inflammation-Induced Cardiac Dysfunction and SARS-CoV2 Infection

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

“…Taken together, our results show apabetalone reduces SARS-CoV-2 infection in vitro and suggest a benefit of apabetalone in COVID-19 pathology arising in ACE2 expressing cell types. Direct infection of the heart remains enigmatic; however, a recent report has described apabetalone-mediated downregulation of ACE2 expression and SARS-CoV-2 infection/propagation in a 2D human cardiac myocyte model [ 52 ] and suggests a benefit of apabetalone in preventing COVID-19-associated cardiac damage. ACE2 converts angiotensin II (Ang II), a hormone that increases blood pressure, into angiotensin (1–7), a vasodilator that lowers blood pressure [ 53 ].…”

“…Through anti-inflammatory properties, apabetalone may favorably suppress hyperimmune processes leading to ARDS and mortality in COVID-19 infections. Further, BETi including apabetalone improved cardiovascular dysfunction induced by inflammatory mediators found prominently in the COVID-19 cytokine storm in a cardiac organoid model [ 52 ] and suggest a benefit on COVID-19-associated inflammation in the heart. Apabetalone may counter overproduction of specific inflammatory mediators that drive the cytokine storm associated with poor outcomes in COVID-19.…”