Binding of the SARS-CoV-2 envelope E protein to human BRD4 is essential for infection

Kendra R. Vann, Arpan Acharya, Suk Min Jang, Catherine Lachance, Mohamad Zandian, Tina A. Holt, Audrey L. Smith, Kabita Pandey, Donald L Durden, Dalia El-Gamal, Jacques Côté, Siddappa N. Byrareddy, Tatiana G. Kutateladze

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1224-1232.e5
Issue number9
StatePublished - Sep 1 2022


  • BRD4
  • ET domain
  • SARS-CoV-2
  • bromodomain
  • envelope E protein

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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