Fig. 1: ATPase activity-competent mSWI/SNF complexes are essential for SARS-CoV-2 infection.
From: Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
a, Schematic of the three mSWI/SNF family complexes, cBAF, PBAF and ncBAF, with subunits colored according to scores in the Vero E6 SARS-CoV-2 CRISPR–Cas9 screen. The average proviral z-scores for each complex are shown. Complex-specific scores represent the sum of two complex-specific subunits, one core subunit and one reader subunit. b, Bar graph depicting the percentage of mNeonGreen-expressing Vero E6 cells (control cells or those with polyclonal CRISPR-mediated knockout of shared or unique mSWI/SNF subunits or ACE2) after infection by icSARS-CoV-2-mNG at an MOI of 1. c, Immunoblot performed in SMARCA4 knockout Vero E6 cells reconstituted with empty vector, WT SMARCA4 or SMARCA4 ATPase-dead mutant (K785R). d, SMARCA4 knockout-complemented and WT Vero E6 cells were infected with icSARS-CoV-2-mNG at an MOI of 1. Infected cells were imaged via fluorescence microscopy (left); mNeonGreen-expressing cell frequency was measured 2 d after infection (right). e, SMARCA4 knockout-complemented and WT Vero E6 cells were infected with SARS-CoV-2 at an MOI of 0.1. Virus titer was measured by plaque assay. PFU, plaque-forming unit. f, SMARCA4 knockout-complemented and WT Vero E6 cells were infected with SARS-CoV-2 (left), HKU5-SARS-CoV-1-S (middle) and MERS-CoV (right) at an MOI of 0.2. Cell viability relative to a mock-infected control was measured 3 d after infection with CellTiter-Glo (CTG). RLUs, relative light units. g, SMARCA4 knockout-complemented and WT Vero E6 cells were infected with VSV pseudovirus (VSVpp): VSVpp-VSV-G; VSVpp-SARS-CoV-2-S (left), VSVpp-SARS-CoV-1-S (middle) and VSVpp-MERS-CoV-S (right). Luciferase relative to the VSVpp-VSV-G control was measured 1 d after infection. Data in b and d–g were analyzed by one-way ANOVA with Tukey’s multiple comparison test. The mean ± s.e.m. are shown. **P < 0.01, ***P < 0.001, NS, not significant. n = 3 biological replicates. Data in c are representative one of three independent experiments.
