RBD-inner face binders (HexaPro-A and -C) consistently show enhanced affinity for B.1.351 HexaPro relative to D614 HexaPro and have less significant loss of affinity for BA.1 HexaPro relative to D614 HexaPro when compared to RBD-top specific binders (HexaPro-H). (a, b) KD value correlation between D614 HexaPro and B.1.351 HexaPro (a) or between D614 HexaPro and BA.1 HexaPro (b). The diagonal line is a theoretical line where the correlating affinities are identical. The areas above and below the diagonal line contain CoVIC IDs that have enhanced and weakened affinity, respectively, compared to D614 HexaPro. If binding by a specific CoVIC ID to B.1.351 or BA.1 is abolished, no data point for that construct is shown. The points are colored according to HexaPro community designations. CoVIC IDs without a community designation are in black. (c, d) Affinity ratios (D614 HexaPro KD / B.1.351 HexaPro KD (c) or D614 HexaPro KD / BA.1 HexaPro KD (d) organized by HexaPro epitope community. A KD ratio >1 indicates an enhanced affinity for variant HexaPro relative to D614 HexaPro; a KD ratio <1 indicates a weaker affinity for variant HexaPro relative to D614 HexaPro. In (c), each vertical line connects a ratio of 1 to the KD ratio for a given CoVIC ID. In (d), each vertical line connects a ratio of 0.01 to the KD ratio for a given CoVIC ID. A gray band in (d) with green borders indicates a range of ratio from 3 to 1/3. Lines without a capping point correspond to CoVIC constructs that had no B.1.351 or BA.1 binding.