Binding of the SARS-CoV-2 envelope E protein to human BRD4 is essential for infection.
Structure
; 30(9): 1224-1232.e5, 2022 09 01.
Article
in English
| MEDLINE | ID: covidwho-1895449
ABSTRACT
Emerging new variants of SARS-CoV-2 and inevitable acquired drug resistance call for the continued search of new pharmacological targets to fight the potentially fatal infection. Here, we describe the mechanisms by which the E protein of SARS-CoV-2 hijacks the human transcriptional regulator BRD4. We found that SARS-CoV-2 E is acetylated in vivo and co-immunoprecipitates with BRD4 in human cells. Bromodomains (BDs) of BRD4 bind to the C-terminus of the E protein, acetylated by human acetyltransferase p300, whereas the ET domain of BRD4 recognizes the unmodified motif of the E protein. Inhibitors of BRD4 BDs, JQ1 or OTX015, decrease SARS-CoV-2 infectivity in lung bronchial epithelial cells, indicating that the acetyllysine binding function of BDs is necessary for the virus fitness and that BRD4 represents a potential anti-COVID-19 target. Our findings provide insight into molecular mechanisms that contribute to SARS-CoV-2 pathogenesis and shed light on a new strategy to block SARS-CoV-2 infection.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Transcription Factors
/
Cell Cycle Proteins
/
Coronavirus Envelope Proteins
/
SARS-CoV-2
/
COVID-19
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Structure
Journal subject:
Molecular Biology
/
Biochemistry
/
Biotechnology
Year:
2022
Document Type:
Article
Affiliation country:
J.str.2022.05.020
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