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. Author manuscript; available in PMC: 2022 Jul 13.
Published in final edited form as: Nat Cell Biol. 2022 Jan 13;24(1):24–34. doi: 10.1038/s41556-021-00821-8

Figure 3: BRD2 inhibitors potently reduce ACE2 levels and SARS-CoV-2 infection.

Figure 3:

a, Transgenic constructs expressed in Calu-3 cells (left). Transcript levels of ACE2 relative to ACTB in Calu3 cells transduced with eGFP-BRD2 truncations in a BRD2 knockdown background (right). Average relative ACE2 gene expression compared to non-transduced cells and standard deviation of n=3 biological replicates are shown. b, Transcript levels of ACE2 relative to ACTB in Calu3 cells treated with BRD2 inhibitors (JQ1 at 10 μM, ABBV-744 at 10 μM and dBET-6 at 200 nM) were quantified at 24 (dark grey bars) and 72 hours (light grey bars) post-treatment. Average ACE2 mRNA levels relative to vehicle of 3 technical replicates are shown from a single experiment. c, Transcript levels of ACE2 relative to ACTB in primary human bronchial epithelial cells treated (NHBE) with BRD2 inhibitors (JQ1 at 10 μM, dBET-6 at 20 nM, ABBV744 at 0.01–10 μM) were quantified at 72 hours post-treatment. Average ACE2 mRNA levels relative to vehicle and standard deviation of n=3 except for the vehicle treated where n=6 biological replicates. d, Transcript levels of ACE2 relative to 18S rRNA in human iPSC-derived cardiomyocytes treated with the indicated concentrations of BRD2 inhibitors were quantified at 72 hours post-treatment. Average ACE2 mRNA levels relative to vehicle treated and standard deviation of n=3 biological replicates for each condition except for the vehicle treated sample where n=6 biological replicates are shown. e, SARS-CoV-2 viral RNA in supernatant measured by RT-qPCR 24 hours post-infection of Calu-3 cells. Infection took place 72 hours after treatment with the indicated concentrations of BRD2 inhibitors. Measurements are the average of n=5 biological replicates. Error bars are the standard deviation. f, Plaque assays in Calu-3 CRISPRi cells treated with increasing concentrations of the BET inhibitors JQ-1 or ABBV-744 infected with SARS-CoV-2 as a function of time post-infection. Average viral titer and standard deviation of six biological replicates are shown except for vehicle and untreated which are three biological replicates.