Severe acute respiratory syndrome coronavirus 2 spike protein non-receptor binding motif epitopes (SARS-CoV-2 S non-RBM epitopes) (SARS-CoV-2 S non-RBM epitopes)

The SARS-CoV-2 spike protein non-receptor binding motif (non-RBM) epitopes are structurally conserved regions of the viral spike glycoprotein that do not directly participate in the interaction with the host ACE2 receptor (Pinto et al., 2020, Nature). These epitopes are located within the N-terminal domain (NTD), the conserved core of the receptor-binding domain (RBD), and the S2 subunit, which is responsible for membrane fusion (Veesler & Corti, 2021, Nature). While the RBM is a frequent target for neutralizing antibodies, it is highly susceptible to mutations that allow the virus to escape the immune response (Harvey et al., 2021, Nat Rev Microbiol). Non-RBM epitopes are typically more conserved across different SARS-CoV-2 variants and other sarbecoviruses, making them vital targets for the development of broadly neutralizing antibodies (bnAbs). Therapeutic agents like Sotrovimab target these conserved sites to maintain efficacy against emerging variants by blocking viral entry or fusion through mechanisms such as steric hindrance or stabilization of the pre-fusion state (Cathcart et al., 2022, Sci Transl Med). These epitopes are therefore central to the design of next-generation vaccines and universal coronavirus therapies.

Other names

Non-RBM epitopesConserved spike epitopesS2 subunit epitopesNTD epitopesRBD core epitopesClass 3 and 4 RBD epitopes

Neutralization of viral entry via steric hindrance of ACE2 binding, inhibition of S1 subunit shedding, or prevention of S2-mediated membrane fusion (Pinto et al., 2020, Nature; Saunders et al., 2022, Front Immunol).