Abstract
The SARS-CoV-2 envelope (E) protein hijacks human BRD4 (bromodomain and extra-terminal domain protein 4). Here, we describe a protocol to characterize the interaction of the acetylated E protein with BRD4 in vivo. We detail steps to use NMR spectroscopy to map the binding interface and include steps to monitor the effect of BRD4 inhibitors in SARS-CoV-2-infected human lung bronchial epithelial cells. This approach could be applied to study interactions involving other viral and human proteins. For complete details on the use and execution of this protocol, please refer to Vann et al. (2022).1.