Direct interaction between human DDX1 and SARS-CoV-2 Nucleocapsid protein is regulated by phosphorylation

The nucleocapsid (N) protein of SARS-CoV-2 is essential for viral replication and transcription, in part through interactions with host proteins. Here, we delineate distinct mechanisms underlying N protein association with human RNA helicases DDX1 and DDX21. Co-immunoprecipitation assays in HEK293 cells modified to express N protein revealed that DDX1 binding requires the N protein serine-arginine (SR) region, as SR deletion markedly reduced interaction. Inhibition of glycogen synthase kinase-3