摘要:SummarySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an epidemic and spread rapidly all over the world. Because the analysis of host factors other than receptors and proteases has not been sufficiently performed, we attempted to identify and characterize host factors essential for SARS-CoV-2 infection using iPS cells and airway organoids (AO). Based on previous CRISPR screening and RNA-seq data, we found that exocyst complex component 2 (EXOC2) is one important host factor for SARS-CoV-2 infection. The intracellular SARS-CoV-2 nucleocapsid (N) expression level was decreased to 3.7% and the virus copy number in cell culture medium was decreased to 1.6% by EXOC2 knockdown. Consistently, immunostaining results showed that N protein-positive cells were significantly decreased by EXOC2 knockdown. We also found that EXOC2 knockdown downregulates SARS-CoV-2 infection by regulating IFNW1 expression. In conclusion, controlling the EXOC2 expression level may prevent SARS-CoV-2 infection and deserves further study.Graphical abstractDisplay OmittedHighlights•EXOC2 is one important host factor for SARS-CoV-2 infection•SARS-CoV-2 infection can be inhibited by EXOC2 knockdown•EXOC2 knockdown downregulates SARS-CoV-2 infection by regulating IFNW1 expression•Cytochalasin D significantly decreased the SARS-CoV-2 infection efficiencyBiological sciences; Immunology; Virology.