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

来源：

BIOMEDICINES | 2021年 / 9卷 / 04期

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

页数：14

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