The N-terminal domain (NTD) of the S protein and the S2 membrane fusion region may be MHC-like structural sites for the challenging battle between the immune system and the virus. Most antibodies that recognize the SARS-CoV-2 S protein are directed against the receptor-binding domain (RBD) . Analysis of the human monoclonal antibody library in the sera of convalescent patients showed that most anti-S antibodies recognize RBD, and a small portion of antibodies recognizes NTD . Some NTD-targeted mAbs can effectively inhibit SARS-CoV-2 infection in vitro; in vivo, the immune system uses neutralization and Fc-mediated effector function activities . Fc receptor cells generally include B cells, killer cells, and macrophages. Compared with neutralizing RBD targeting antibodies that recognize multiple non-overlapping epitopes, effective NTD targeting neutralizing antibodies appear to target a single supersite(42): N17, N74, N122, and N149. However, popular variants will partially or completely escape the neutralization mediated by human monoclonal antibodies (mAb) targeting the antigen supersite (site i) . The variants include B.1.1.7, B. .1.35, and P.1 pedigree. It is difficult for immune system antibodies to neutralize part of the mutation sites in the N-terminal domain and the fusion region of the S2 membrane.