Bromodomain and extraterminal protein inhibitor, apabetalone (RVX-208), reduces ACE2 expression and attenuates SARS-CoV-2 infection in vitro
| Autor: | Dalia Moore, Jan O. Johansson, Audrey L Smith, St Patrick Reid, Ewelina Kulikowski, Michael O. Sweeney, Stephanie C. Stotz, Abenaya Muralidharan, Norman C.W. Wong, Dean Gilham, Li Fu, Dalia El-Gamal |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
QH301-705.5 Medicine (miscellaneous) RVX 208 030204 cardiovascular system & hematology Biology Article General Biochemistry Genetics and Molecular Biology angiotensin-converting enzyme 2 (ACE2) BET inhibitor 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell surface receptor Medicine BET proteins Epigenetics Biology (General) chemistry.chemical_classification Infectivity apabetalone business.industry SARS-CoV-2 COVID-19 Virology In vitro Bromodomain 030104 developmental biology Enzyme chemistry Cancer research business Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Biomedicines Volume 9 Issue 4 Biomedicines, Vol 9, Iss 437, p 437 (2021) |
| DOI: | 10.1101/2021.03.10.432949 |
| Popis: | 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 antiviral agents. Taken together, our study supports further evaluation of apabetalone to treat COVID-19, either alone or in combination with emerging therapeutics.Graphical Abstract |
| Databáze: | OpenAIRE |
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