Table 8.
Seven major epitope groups of antibodies targeting SARS-CoV-2 RBD#
| Class# | Other epitope grouping a |
Block ACE2 | Binding location | RBD confor-mation | Key binding residues b,c | Mutations that affect binding | Mutations or variants mostly resisted | Other comments | Antibodies in groupd |
|---|---|---|---|---|---|---|---|---|---|
| RBD-1 |
B-1, Y-RBS-A |
Yes | Largely overlap RBM | Open only | R403, K417, D420, Y421, Y453, L455, A475, N501 |
Quite variable; Beta, Gamma; K417N/T e |
Alpha, Epsilon, Delta | Amongst most potent but also most susceptible to mutations; Fully occupy all three RBDs per spike; often cross-link spike trimers | CB6, CC12.3, C102, BD-629, P4A1, etc |
| RBD-2 |
B-2, Y-RBS-B |
Yes | Shifted toward the peak of RBM | Open only | (K417), L455, F456, E484, G485, F486, N487, Q493 | Beta, Gamma; combination of Y453F, E484K/Q, F486L, N501T | Alpha, Epsilon, Delta | Largest group of mabs; amongst most potent but also most susceptible to mutations; tend to bind bivalently within one spike | S2E12, REGN10933, AZD8895, B1-182.1, C144, HLX70, LY-CoV555, CT-P59, CA521, COVA2-39, CV07-250, Fab2-04 |
| RBD-3 | NA | Yes | RBM; Bind center of ACE2 binding site near “mesa” | Open only | ND | N501T/Y, E484K | K417N | Competes with both ACE2 and CR3022; IgGs can cross-link spikes; some IgGs will bind bivalently intraspike | ADI-56046 [437] |
| RBD-4 |
B-2, Y-RBS-C |
Yes (4A)/no (4B) | Outer face of RBD; bind toward the outer edge of the RBM | Open or closed | R346, K444, G446, N450, E484, Y489, Q493 |
E484K and/or L452R; B.1.429 (epsilon) |
L455, F456, E484, F490, Q493 |
Some can crosslink spike trimers in solution |
P2B-2F6, CV07-270, MW05, BD-368-2, AZD1061, BG10-19 |
| RBD-5 |
B-3, Y-RBS-D |
No | Outer face of RBD; toward S309 site | Open or closed |
T345, R346; N343 (5B); L452R |
Few residues | Broad resistance against variants | Some can cross-link spikes, which leads to potent neutralizing activity | REGN10987, LY-1404, C110, S309, C135, 47D11 |
| RBD-6/7 |
B-4, Y-CR3022 site |
Yes (6, 7A); no (7B, 7C) | Bind inner face of RBD; access cryptic epitope | Two RBDs must be open | Y369, T376, S383, T385, (D427, D428) | ND | ND | Generally less potent; tendency to cross-link spike trimers; RBD-6 epitope extends closer to RBM | COVA1-16, MW06, H014, S2X259, CR3022, EY6A |
B-1, etc., Barnes et al., Class 1 antibodies, etc. [276], NA not applicable, ND no data, RBD receptor binding domain, RBM receptor binding motif, Y-RBS-A, etc., Yuan et al., RBS epitope grouping A, etc. [277]
aAs guided by the epitope groupings by Hastie et al. [290]
bGroupings by Barnes et al. [276] (B) and Yuan et al. [277] (Y)
cResidues included in the epitopes of the majority of group members. Those residues in parentheses are more variably included in the epitope
dSee Figs. 6A, B, 7A, and B for more information. Note that many other antibodies not included in this paper also fall into these epitope groups
e reference [322]