Fig. 2: Host dependency factors and pathways of SARS-CoV-2 in lung cells revealed by genome-wide LOF screening.

a, Protein–protein interaction network for top 100 enriched hits identified in the CRISPR LOF 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. AKT, AK strain transforming; IFN, interferon; MAPK, mitogen-activated protein kinase; SWI/SNF; SWItch/Sucrose Non-Fermentable. b, Pathway analysis of top 100 enriched hits indicates significantly overrepresented pathways with putative proviral roles. Circle size indicates the number of genes within each pathway, color indicates FDR of pathway enrichment. c, Individual TCID50 validation for KO of the top five enriched hits from our LOF screen plus additional hits of interest. Calu-3 cells were infected with SARS-CoV-2 at an MOI of 0.05 for 48 h, each gene was targeted with at least two separate guides. Dotted lines indicate the limit of detection (LOD) of the assay as well as the NTG average for four separate guides. Significance was not calculated because n = 2 biological replicates.