Fig. 2: SARS-CoV-2 Omicron is inefficient in using TMPRSS2.

a, HEK293T cells were transfected with ACE2 or co-transfected with ACE2 and TMPRSS2, followed by transduction with pseudoviruses carrying the spike protein of SARS-CoV-2 WT, Alpha, Beta, Delta or Omicron at 24 h.p.i. Pseudovirus entry was quantified by measuring the luciferase signal. n = 9 (Delta) and n = 10 (WT, Alpha, Beta and Omicron). Fold changes in the luciferase signal were normalized to the mean luciferase readouts of cells with only ACE2 overexpression. b, VeroE6 and VeroE6-TMPRSS2 cells were transduced with pseudoviruses carrying the spike protein of SARS-CoV-2 WT, Alpha, Beta, Delta or Omicron. Pseudovirus entry was quantified by measuring the luciferase signal. n = 6. Fold changes in the luciferase signal were normalized to the mean luciferase readouts of VeroE6 cells. c, d, VeroE6-TMPRSS2 cells were pretreated with 1 μM, 25 μM or 50 μM camostat or DMSO for 2 h followed by transduction with pseudoviruses carrying the spike protein of SARS-CoV-2 WT, Alpha, Beta, Delta or Omicron (c) or challenged with the indicated authentic SARS-CoV-2 variants at 0.1 m.o.i. (d). Pseudovirus entry was quantified by measuring the luciferase signal of the cell lysates at 24 h.p.i. n = 6. The amount of viral subgenomic envelope RNA in collected cell lysates at 24 h.p.i. was determined using quantitative PCR with reverse transcription (RT–qPCR). n = 7 (Delta, Omicron and Omicron(R346K) at 1 µM, 25 µM and 50 µM) and n = 6 (all other samples). Data are mean ± s.d. from the indicated number of biological replicates. Statistical significance was determined using two-way ANOVA (a–d); where multiple comparisons were performed among different groups, P values were adjusted using Tukey’s multiple-comparison test; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; NS, not significant. Data were obtained from three independent experiments. Each data point represents one biological replicate.

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