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

被引:25
|
作者
Gilham, Dean [1 ]
Smith, Audrey L. [2 ]
Fu, Li [1 ]
Moore, Dalia Y. [2 ]
Muralidharan, Abenaya [3 ]
Reid, St. Patrick M. [3 ]
Stotz, Stephanie C. [1 ]
Johansson, Jan O. [1 ]
Sweeney, Michael [1 ]
Wong, Norman C. W. [1 ]
Kulikowski, Ewelina [1 ]
El-Gamal, Dalia [2 ]
机构
[1] Resverlogix Corp, 300,4820 Richard Rd SW, Calgary, AB T3E 6L1, Canada
[2] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, 986805 NE Med Ctr,BCC 4-12-396, Omaha, NE 68198 USA
[3] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, 985900 Nebraska Med Ctr, Omaha, NE 68198 USA
关键词
COVID-19; SARS-CoV-2; BET proteins; apabetalone; angiotensin-converting enzyme 2 (ACE2); CARDIOVASCULAR-DISEASE; BET; MODULATION; PATHWAYS;
D O I
10.3390/biomedicines9040437
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页数:14
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