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Evidence of a Geographic Epicenter in Pemivibart (VYD2311) Escape: Validation of 817 Natural Isolates Harboring the Complete XFG-Loss Motif (K444T + N460K + F486P)

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posted on 2025-12-03, 12:39 authored by Tahir BhattiTahir Bhatti
<p dir="ltr">This dataset provides genomic confirmation that the complete pemivibart (VYD2311) escape architecture has emerged and stabilized within a dominant geographic region. From a master archive of 9,398,268 global SARS-CoV-2 spike amino acid sequences (January 2020 - September 2025), we identified <b>817</b> (Previosuly 811 now we have additional 6 more sequences) natural isolates carrying the full 5/5 escape haplotype (R346T + S371F + K444T + N460K + F486P) the mutational ceiling for therapeutic evasion. All 817 isolates inherently contain the XFG-loss motif (K444T + N460K + F486P), which disrupts the XFG-binding arm of pemivibart’s dual-epitope architecture.</p><p><br></p><p dir="ltr">Geographic attribution of isolate headers (e.g., Country/Isolate/Year) reveals that <b>88.6</b>% of global 5/5 isolates originate from a single high-surveillance nation (USA), with the remainder distributed across Switzerland, Denmark, and England. The temporal distribution (2 isolates in 2022, 646 in 2023, 168 in 2024, and 1 in 2025) confirms sustained emergence and fixation within this region, culminating in the identification of the sole 2025 5/5 genome (KP.3 lineage).</p><p><br></p><p dir="ltr">Sequences were extracted directly from the reference-aligned master dataset (Wuhan-Hu-1: YP_009724390.1) using strict quality filters (≥95% spike coverage, no internal stop codons, unambiguous residue calls). Each entry is provided as a compressed amino acid FASTA (.fasta.zst) file, preserving original headers for auditability.</p><p><br></p><p dir="ltr">This evidence confirms that pemivibart resistance is not diffuse but concentrated in a defined epidemiological epicenter, where selective pressures have driven the complete dismantling of the therapeutic epitope.</p><p><br></p><p dir="ltr"><b>Note</b>: This dataset supports the conclusions of the associated manuscript “<b><u>Variant-Agnostic Emergence and Stabilization of the Pemivibart (VYD2311) Escape Architecture in SARS-CoV-2.</u></b>”</p><p dir="ltr">Study by: TahirHB@Hotmail.Com</p>

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