Updated project metadata. We sought to compare differences in the SARS-CoV-2 virus-human protein interaction networks between mutated (from the SARS-CoV-2 variants of concern) and wild-type viral proteins. Here, we ectopically expressed 2x-strep-tagged constructs encoding mutant or wild-type SARS-CoV-2 viral proteins in HEK293T cells followed by affinity purification mass spectrometry (APMS). This allowed us to quantify differences in protein-protein interactions attributable to mutations present within SARS-CoV-2 variant proteins.