These computationally successful candidates were obtained by optimizing initial parent designs and complementary DWBEL and ADV docking algorithms. The first most important step was an intensive search for an specific initial 2D molecular parent from which to generate many derivatives whose ADVconformers would computationally cross-fit the gpGVHSV R4-TrD interface. After numerous testing alternative manual 2D designs, the highest docking affinities at low µM ranges were predicted only by 3-fold symmetry star-shaped ADVconformers. Most of the higher affinity star-shaped conformers cross-docked the 3-chains which formed the R4-TrD inner-cavity of the gpGVHSV pre-fusion trimer, rather than docking only to 1 or 2 chains. Aiming to improve their µM affinities and to maintain their cross-targeted R4-TrD, the cn30 was selected for further work. Tens of thousands of raw-children derivatives were randomly generated from the cn30 parent using DWBEL co-evolution. During their co-evolution, the gpGVHSV -cn30 cavity was employed to screen for those best conformers fitting all the druglike chosen criteria. Thousands of non-toxic children conformers with specific molecular weights, hydrophobicity and best-cross-fitting the R4-TrD interface were generated. The new children affinity improvements and maintenance of their crosstargets were confirmed by applying the ADV independent algorithm. Hundreds of unique top-children ADV-conformer candidates predicting affinities in the low nanoMolar range and cross-fitting the R4-TrD interface were identified. All those top-children predicted molecular conformers with many small variations of 3-arm star-shaped 2 main scaffolds, suggesting that high-affinity cross-docking of the 3 chains of trimeric gpGVHSV R4-TrD, could be the best target to propose to interfere with fusion transitions. Although with similar limitations, these results were analogous to those predicted before for the SARS-CoV2 trimer employing also coevolution strategies . Some of the limitations to the predicted molecules, include: a) hypothetical similarities between crystallographic-gpGVSV and its modeled-gpGVHSV, b) one parent 2D molecule and one R4-TrD targeted cavity were studied among many other possibilities (i.e., Bc / Sc, monomers, dimers, transition intermediates, etc), c) exploration of resistant mutations remains hypothetical, d) no consideration of R4-TrD side-chain amino acid flexibilities has been studied, and e) lack of experimental evidences, such as binding to recombinant gpGVHSV, and/or inhibition of fusion (syncitia) or infectivity by VHSV in vitro / in vivo assays. On the other hand, despite the application of several improvements to the DWBEL-ADV algorithms by previous work in other protein / ligand pairs (Table ) , further targeting the gpGVHSV with alternative and deeper explorations, could add more penetration into the enormous chemical space . Most probably such efforts would increase the probabilities to identify distinct drug-like molecules, 3D conformers and scaffolds docking gpGVHSV.Therefore, up to now all that can be said is that these top cross-docking conformers predicted high-affinity contacts to some of the gpGVHSV amino acids implicated in one of the most probable earlieststeps of trimer fusion transitions.