(a) Experimental diagram: the viral replication kinetics were measured in Calu-3 cells infected with SARS-CoV-2 (Delta variant of concern, pangolin linage: B.1.617.2) with 0.5 MOI of viral titer and treated with JQ1 or OTX015. (b) Representative immunofluorescence images of infected (or uninfected negative control) Calu-3 cells probed with antibodies against the Spike glycoprotein of SARS-CoV-2 (green) in the absence (positive control) or presence of JQ1 and OTX015 at the indicated concentrations. Scale bar, 100 μm for all panels. (c) Percent inhibition of SARS-CoV-2 infection in Calu-3 cells treated with JQ1 and OTX015 at the indicated concentrations. (d) Cell viability in compound treated and SARS-CoV-2 infected Calu-3 cells. Data in (c, d) represent mean of three replicates, and error bars represent SEM. n=3 Cells were from the same frozen stock, and experiments were performed using the same plate on the same day. (e, f) Inhibition of SARS-CoV-2 replication in Calu-3 cells treated with JQ1 (e) or OTX015 (f). BRD4 inhibitor mediated effects on SARS-CoV-2 viral load were quantified in the culture supernatant using RT-qPCR and plotted as % inhibition of viral replication. Data in (e, f) represent mean of three independent measurements, and error bars represent SEM. n=3