text: SARS CoV 2 Nucleocapsid protein attenuates stress granules and interacts with mRNAs to impair host stress response Severe acute respiratory syndrome coronavirus 2 SARS CoV 2 nucleocapsid N protein is essential for viral replication making it a promising target for antiviral drug and vaccine development SARS CoV 2 infected patients exhibit an uncoordinated immune response however the underlying mechanistic details of this imbalance remain obscure Here starting from a functional proteomics workflow we catalogued the protein protein interactions of SARS CoV 2 proteins including an evolutionarily conserved specific interaction of N with the stress granule resident proteins G3BP1 and G3BP2 N localizes to stress granules and sequesters G3BPs away from their typical interaction partners thus attenuating stress granule formation We found that N binds directly to host mRNAs in cells with a preference for 3 UTRs and modulates target mRNA stability We show that the N protein rewires the G3BP1 mRNA binding profile and suppresses the physiological stress response of host cells which may explain the imbalanced immune response observed in SARS CoV 2 infected patients 