CRISPRing for host genes regulating SARS-CoV-2

In this preprint, Wei et al. screened the African green monkey genome using CRISPR–Cas9 for genes involved in SARS-CoV-2 infection and cell death. Surprisingly, SARS-CoV-2, which replicates in the cytosol, depends on a large number of host genes that function in the nucleus. Amongst the crucial genes, the SWI/SNF chromatin remodelling complex, several TGFβ signalling components and the alarmin HMGB1 were proviral, whereas the histone H3.3 complex was antiviral, highlighting the importance of epigenetic regulation in antiviral responses. Treatment of cells with small-molecule inhibitors of the SWI/SNF complex and of the TGFβ signalling pathway protected against SARS-CoV-2 infection. Further studies will need to investigate how these host genes regulate infection and whether these inhibitors could be used therapeutically.