<figure><img src="image_77.png" /><figcaption>Figure S6. Validation and fitness of VIR-7229 escape mutations, related to Figures 5 and 6</figcaption></figure>

(A) VIR-7229-mediated neutralization of SARS-CoV-2 pseudoviruses carrying mutations that were observed as DMS binding escapes in at least one strain background, plus F456L. Mutations were tested in different strain backgrounds, as indicated by bar color. Mutations are annotated as (a) total counts in the GISAID database as of May 8, 2024, (b) fold-change reduction in ACE2 affinity in the XBB.1.5 background evaluated by DMS⁶⁴ (available from https://tstarrlab.github.io/SARS-CoV-2-RBD_DMS_Omicron-XBB-BQ/RBD-heatmaps/), (c) impact on pseudovirus infectivity (assessed by evaluating the viral titer in comparison with the titer of respective unmutated backbone quantified in parallel; - indicates titers within 5-fold, ↓ indicates a titer more than 5-fold reduced in at least one backbone, ↓↓ indicates a titer more than 5-fold reduced in at least two backbones; see also Data S5), (d) minimum number of nucleotide changes required for the mutation to occur, and (e) the RBD background where the mutation was observed as a binding escape in the DMS experiment. ND, not determined; na, not applicable. See also Data S1.

(B) VIR-7229-mediated neutralization of SARS-CoV-2 pseudoviruses carrying mutations that were observed during the EG.5 rVSV resistance selection experiment. Strain background is indicated by bar color. For L455W, JN.1 is also the BA.2.86 background (JN.1 = BA.2.86 + L455S). Mutations are annotated as in (A), as well as by counts in the +F456L background in the GISAID database as of May 8, 2024. See also Data S1.

(C) VIR-7229-mediated neutralization of SARS-CoV-2 pseudoviruses carrying a set of epitope mutations below 0.005% frequency in GISAID but accessible by a single nucleotide change from wild-type sequences. Mutations were tested in either the BQ.1.1 or XBB.1.5 background; some mutations were tested in both backgrounds. See also Data S1.