Tiered Structural Analysis of MERS-CoV Spike Residues: Prioritizing DPP4-Contact Sites for Zoonotic Risk Assessment and Immune Escape Signatures

Building on our previous validation of DPP4-contact residues (511, 539) and immune escape signatures (499, 534, 553) in MERS-CoV Spike, this update introduces a tiered structural analysis to systematically prioritize residues based on their proximity and functional importance to the DPP4 interface. Using PyMOL, we categorized residues into five tiers: Tier 1: Core DPP4-contact residues (e.g., 511, 539) with direct binding roles. Tier 2–5: Progressively peripheral residues, ranked by their spatial and evolutionary relevance. This approach enhances reproducibility and precision in identifying high-risk residues for zoonotic spillover and therapeutic targeting.