The AutoDockVina (ADV) algorithm (PyRx-0.98/1.0 package) was used to: i) quantify in ~ nM the DWBEL non-toxic fitted-children affinities, ii) identify PyMol amino acid contacts on ADV docked protein-children complexes and iii) confirm the targeted cavities on F trimers. The ADV algorithm was selected for docking because of its higher accuracies when compared to other docking programs and its most recent improvements . The PyRx/Obabel/ADV algorithms were adapted to large scale docking by home-scripts 47 . As mentioned above, the DWBEL non-toxic fittedchildren sdf files required DW mmff94s+ minimization to preserve their 2D geometries during ADV . Several ADV grids were used for docking. A wide grid of 60x60x60 Å centered to the PyMol / centerofmass surrounding most of the F homotrimers was initially employed for blind-docking. Both 20x20x20 Å and 13x13x13 Å grid, centered at 19x19x19 Å (from the F centerofmass), were employed to restrict docking to the drugsite cavities. Duplicates and/or triplicates for selected mutations were used to confirm their affinities and reduce variations between runs due to their abundant random rotatable bonds (± 2.5 Kcal/mol). After ADV docking, only the best conformer of each non-toxic fitted-children was selected for additional calculations. The output ADV docking-scores in -Kcal/mol were converted to ~ nM affinities by the formula, 10 9 *(exp (Kcal/mol/0.592) ). A, F2p27F1+TM+CT homotrimer prefusion side-view . B, F2F1+TM+CT homotrimer postfusion side-view . C, F-wt truncated homotrimer crystallographic model side-view . D, Cl bottom-view of its central cavity . Yellow cylinders, Hydrophobic α-helices containing part of the HRB heptad-repeats (~444-485 residues) Green cylinders, transmembrane α-helices (485-514). Blue cylinders, Hydrophobic α-helices containing part of the HRA heptad-repeats (~173-182 residues) . Green spheres, amino terminal amino acids of F1 and/or F2 (p27 included) Red spheres, mapping of fusion-inhibitor drugs nearby residues 140, 486-489 (drug-site) ii) Red sticks, side-chains at the bottom-surface surrounding the drug-site (L138I, L141W, G143S, V144A, T323A, I379V, V384I, D388Y, D392G, K394R, M396I, T397S, S398L, K399N, T400I, D401E, I474T, V482A, S509I).