Fig. 6: Impact of the identified antiviral genes on coronaviruses SARS-CoV-2, HCoV-229E and MERS-CoV and orthomyxovirus influenza A.

Calu-3-dCas9-VP64 (a–e) or Calu-3-Cas9 (f) cells were stably transduced to express 2 sgRNAs (g1, g2) per indicated gene promoter (a–e) or coding region (f), or negative controls (CTRL) and selected for at least 10–15 days. a, Cells were infected with SARS-CoV-2 bearing the mNG reporter and the infection efficiency was scored 48 h later by flow cytometry. b, Cells were infected with HCoV-NL63, and infection efficiency was scored 5 days later by RT-qPCR. c, Cells were infected with HCoV-229E-Renilla, and 48–72 h later, relative infection efficiency was measured by monitoring Renilla activity. d, Cells were infected with MERS-CoV, and 16 h later, the percentage of infected cells was determined using anti-Spike IF staining followed by microscopy analysis (n = 10 fields per condition). e, Cells were infected with influenza A virus bearing the NLuc reporter, and 10 h later, relative infection efficiency was measured by monitoring NLuc activity. f, Cells were infected with SARS-CoV-2 bearing the mNG reporter, and the infection efficiency was scored 48 h later by flow cytometry. The mean and s.e.m. of three or more (a–e; except for panels a (JADE3, OR1N1 KO), d (MAFK1 g1, ATAD3B g2, ZNF572 g2 KO) and e (ATAD3B, ATP6V0A2, ZNF572 KO) n = 2) or two (f) independent experiments are shown. Statistical significance was determined by a two-sided t-test (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001) (a–e). Exact numbers and P values are indicated in Supplementary Data 17. The red and dark red dashed lines indicate 50% and 80% inhibition (a–e), and the green and dark green dashed lines indicate 150% and 300% increase in infection efficiency, respectively (f).