The gpGVSV homotrimer ectodomain sequences implicated in fusion were extracted from 5I2S and 5I2M models in PyMol, their α-helices were drawn as cylinders (gpGVSV whole ectodomains at Figure ). The corresponding folds, Cysteins and trimers in gpGVHSV were similar but differed in their amino acid sequences (Table Searching for appropriated 2D-molecules to start DWBEL, numerous preliminary ADV docking attempts resulted in limited conformer affinities to R4-TrD predicting docking to 1 or 2 chains of gpGVHSV. Only a few manually designed starshaped conformer candidates cross-docked the inner cavity at the level of R4-TrD. Such candidates were also chosen because they not only cross-docked the 3 chains but also occupied a central position in the inner cavity of the gpGVHSV prefusion trimer. Among a few other possibilities, the cross-docked conformer number 30 (cn30, chemical formula: C24H45N3O6), was selected for further work. The cn30 corresponded to an star-shaped 2D-molecule of a central cyclohexane with 3 symmetrical arms of 4 carbons each, ended by amine / carboxylic groups (Alanines), of 471 g/mol of molecular weight and -3.3 LogP hydrophobicity (Figure , up). In particular, the corresponding conformer of cn30 cross-docked the A,B,C chains of gpGVHSV implicating most of their 67 E, 68 F, 71 I, 72 N, 302 L 303 N, 304 H, 307 T (amino acids defining the gpGVHSV R4-TrD) with low affinities around ~ 4400 nM. Therefore, to explore whether such affinities could be increased, DWBEL coevolutions were attempted. To star DWBEL co-evolutions, the cn30 was chosen as parent to generate large numbers of raw-children and the gpGVHSV-cn30 ADV docked complex cavity was chosen as target to select the best-fitting children DWBEL-conformers. As DWBEL controls for specificity, one cn30 parent was also chosen by maintaining constant its central cyclohexane-4 carbon arms, thus restricting their co-evolution to its terminal Alanines (fixed or restricted cn30).