SARS-CoV-2 spike protein receptor-binding domain and secondary non-neutralizing epitope (SARS-CoV-2 S-RBD/NNE)

The SARS-CoV-2 spike protein receptor-binding domain (RBD) is the primary target for neutralizing antibodies as it mediates the virus's attachment to the human ACE2 receptor (PubMed: 32221306). However, targeting the RBD alone can lead to viral escape through mutations, prompting the inclusion of secondary non-neutralizing or weakly neutralizing epitopes in therapeutic strategies (PubMed: 33619132). These secondary epitopes, often located in the N-terminal domain (NTD) or conserved regions of the S2 subunit, may not directly block viral entry but can trigger potent immune responses (PubMed: 34525431). Specifically, antibodies binding to these sites can facilitate viral clearance via Fc-receptor-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (PubMed: 33514628). This dual-targeting approach, often realized through antibody cocktails or bispecific antibodies, aims to provide broader protection against emerging variants and enhance the overall antiviral activity (PubMed: 34210987). By combining direct neutralization with immune-mediated clearance, these therapies offer a more robust defense against COVID-19 (PubMed: 32155444).

Other names

SARS-CoV-2 S-RBDSpike protein RBDS1 subunitNon-neutralizing spike epitopesWeakly neutralizing epitopesConserved spike epitopes

Neutralization of viral entry by blocking ACE2 binding via the RBD and recruitment of immune effector functions (ADCC/ADCP) through secondary epitope binding.