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.
【저자키워드】 COVID-19, SARS-CoV-2, Angiotensin-converting enzyme 2 (ACE2), BET proteins, apabetalone, 【초록키워드】 ACE2, pandemic, SARS-COV-2 infection, Infection, in vitro, outcome, angiotensin-converting enzyme 2, DPP4, viral infectivity, cells, Antiviral agents, Patient, inhibitor, expression, Epigenetic, Combination, cell surface receptor, host cell, Support, SARS-CoV-2 entry, treat, CD26, manipulation, BET, IMPROVE, involved, reported, inhibit, modulate, comparable, downregulate, 【제목키워드】 ACE2, bromodomain, RVX-208,