Fig. 4: Host restriction factors and pathways of SARS-CoV-2 in lung cells revealed by GOF screening.

a, Protein–protein interaction network for top 100 enriched hits identified in the CRISPR GOF screen based on STRING analysis. Solid lines between genes indicate direct interaction, dashed lines indicate indirect connections. Nodes are color-coded by functional groups and scaled according to screen enrichment RRA score. GPCR, G-protein-coupled receptor; PRR, pattern recognition receptor. b, Pathway analysis of top 100 enriched hits indicates significantly overrepresented pathways with putative antiviral roles. Circle size indicates the number of genes within each pathway, color indicates FDR of pathway enrichment. c, Individual validation of the effect of transcriptional upregulation of the top five enriched putative antiviral hits from the GOF screen, measuring SARS-CoV-2 viral titer by TCID50. Error bars denote mean ± s.e.m., n = 3 biological replicates. The dotted lines indicate the LOD of the assay as well as the NTG average. Significance was determined with individual two-sided t-tests between each GOF line and NTG. NS, not significant; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.