Experimental Validation of Pemivibart (VYD2311) Escape in Four Clinically Flagged SARS-CoV-2 Genomes: Evidence of Functional Resistance Despite Pipeline Classification Artifacts

This dataset documents a targeted re-evaluation of four SARS-CoV-2 sequences (SRR36291578, SRR29992357, SRR28971845, ERR15656806) previously flagged in our surveillance systems as exhibiting pemivibart (VYD2311) resistance. Using a custom, codon-resolution bioinformatic pipeline, we confirm: F486P in 2/4 samples (SRR29992357, SRR28971845)F456L in 1/4 samples (ERR15656806)S371F (non-escape) in all 4 samplesNo canonical escape mutation in SRR36291578Critically, our initial pipeline underclassified resistance due to two key design limitations: Inclusion of S371F as an escape mutation (biologically irrelevant for VYD2311)Overly stringent resistance threshold (requiring ≥3 mutations, whereas ≥1 of F456L/K444T/F486P is sufficient per FDA EUA and neutralization data) Upon manual BAM inspection and biological reinterpretation, 3 of 4 samples harbor validated pemivibart escape mutations, consistent with prior global trends reported in our larger dataset (DOI: 10.5281/zenodo.17201049). This work demonstrates: The high specificity of F456L/F486P as resistance markersThe risk of false-negative classification when bioinformatic rules do not reflect therapeutic thresholdsThe ongoing relevance of pemivibart escape monitoring, even as variant prevalence shifts. Files included: pemivibart_results/ (full pipeline output)manual_validation_notes.txt (IGV screenshots and codon-level summaries)corrected_classification_summary.csvMethods: BWA-MEM alignment → iVar/bcftools variant calling → codon-based escape analysis (NC_045512.2 coordinates)Reference: Wuhan-Hu-1 (NC_045512.2)Therapeutic context: Pemivibart (VYD2311) FDA EUA, 2024 Study by: Tahir HB