Fig. 5: SMARCA4 is required for ACE2 expression and sarbecovirus susceptibility in primary human cells.
From: Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
a, Schematic of SMARCA4/2 ATPase inhibitor treatment and virus infection in primary HBECs. b–e, HBECs were pretreated with 2.5 and 5 μΜ Comp12 for 4 d and then infected with SARS-CoV-2 (b), HKU5-SARS1-S (c), MERS-CoV (d) and IAV (e). Virus replication was measured by plaque assay and/or RT–qPCR. f, HBECs were pretreated with 2.5 μΜ Comp12 for 4 d and then infected with SARS-CoV-2 WA1 or E802D virus at an MOI of 0.5. The virus titer was measured using plaque assay. Remdesivir was added right after infection. g, ACE2 expression was measured using RT–qPCR; SARS-CoV-2 replication was measured using a plaque assay after virus infection in HBECs pretreated with 2.5 μΜ of the indicated compounds for 4 d. h, hPSC-derived pneumocyte-like cells were pretreated with Comp12 for 2 d and then infected with SARS-CoV-2 at an MOI of 0.1. i,j, Infectivity was measured by the accumulation of viral nucleoprotein in the nucleus of the cells 2 d after infection. ACE2 expression and SARS-CoV-2 infection were measured in HIEs (i) and MIEs (j) pretreated with 2.5 μΜ of the indicated compounds for 3 d except remdesivir, which was added right after virus infection. k, Model depicting the mechanism of mSWI/SNF complex-mediated regulation of ACE2 expression and SARS-CoV-2 entry. In b, c, d, f, g and i, the dashed line indicates the limit of detection. Data in b–j were analyzed using a one-way ANOVA with Tukey’s multiple comparisons test. The mean ± s.e.m. are shown. **P < 0.01, ***P < 0.001, ****P < 0.0001, n = 3 biological replicates.
