Global Catalog of SARS-CoV-2 Receptor-Binding Domain (RBD) Haplotypes (Spike 319 - 541), 2020 - 2025

This dataset presents a comprehensive, population-scale analysis of the SARS-CoV-2 spike protein’s Receptor-Binding Domain (RBD), defined as residues 319 - 541 (Wuhan-Hu-1 reference, GenBank YP_009724389.1). Built from 9.4 million global viral genomes (2020 - 2025), it provides a real-time map of natural variation across the RBD, a region of critical importance for ACE2 binding, immune recognition, and therapeutic targeting. To stress-test the resilience of this domain we: Extracted all naturally occurring RBD haplotypes (n = 435,723),Quantified yearly frequencies of escape-associated substitutions at 16 key positions,Tracked erosion of reference residues over time,Profiled codon usage dynamics as a proxy for host-driven selection,Mapped the observed vs. theoretical escape landscape across functionally critical sites. Our analysis reveals that the RBD has undergone rapid, convergent evolution, with a small set of high-fitness haplotypes dominating global circulation by 2023. Notably, residues previously implicated in high-affinity binding to human receptors and neutralizing antibodies show near-complete replacement in contemporary lineages suggesting that the functional integrity of certain epitope architectures may no longer reflect the in vitro reference. This resource is intended for: Viral evolutionary biologists,Therapeutic developers assessing epitope durability,Public health agencies monitoring variant risk,Computational researchers modeling immune escape. All data is provided in open, machine-readable formats (FASTA, TSV, CSV), with full reproducibility. Analyses were conducted independently by Tahir HB using command-line bioinformatics infrastructure and population-genomic principles. No external funding or institutional affiliation was involved.