Beyond the Mutation Abyss: Revisiting SARS-CoV-2 Receptor-Binding Domain Evolution from ACE2 Binding Optimization to Immune Epitope Remodeling.

In contrast, Omicron variants ( n = 8) showed no significant charge–binding relationship (ρ = −0.27, p = 0.518), and the difference between era-specific correlations did not reach statistical significance (Fisher z p = 0.184), indicating a trend rather than definitive evidence for a discrete shift in binding determinants.

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