The Nipah virus (NiV) attachment glycoprotein G mediates host-cell entry by binding to ephrin-B2 and ephrin-B3 receptors. To design compact antiviral binders, we used the BindCraft generative-design pipeline to create mini-protein (65–120 aa) candidates against functionally validated regions of the G ectodomain (Chain A): (1) residues 201–300, critical for single-domain antibody n425. Bthis region was prepared in Maestro (Schrödinger) and energy-minimized with the OPLS4 force field before design. BindCraft backbone generation, ProteinMPNN sequence optimization, AlphaFold2-multimer prediction, and Rosetta refinement produced compact binders predicted to form stable interfaces. We applied BindCraft, combined with ProteinMPNN, AlphaFold2, and Rosetta, to design de novo binders against experimentally supported G regions (450–603), using PDB 2VSM as structural references. Structural Rationale and Target Selection Region 1: Residues 200–300 (Chain A positions 217, 231, 257–259, 264–270) • This region sits on the β-propeller head of G and forms part of tn45 binding site (8XPY). • These positions exhibit structural roles in shaping the local docking surface and appear to influence loop flexibility—characteristics favorable for small peptide or loop-oriented mini-protein engagement. Target Preparation Before binder design, each target region was refined in Maestro (Schrödinger 2024-4): 1. Imported Chain A coordinates from 2VSM 2. Assigned protonation states at pH 7.0 and optimized H-bonding networks via Protein Preparation Wizard. 3. Performed energy minimization with the OPLS4 force field until convergence (RMSD < 0.3 Å). 4. Verified absence of steric clashes and ensured solvent accessibility of all hotspot residues.