A schematic diagram shows that two residues change in SARS-CoV-2 N protein trigger NF-κB inhibition. The SARS-CoV-2 N protein competitively binds TAB2/3 and inhibits the formation of the TAK1–TAB2/3 complex, thereby exerting its inhibitory effect on the NF-κB pathway. In contrast, the SARS-CoV N protein interacts with TAB2/3 without interfering with the assembly of the TAK1–TAB2/3 complex.