In this preliminary work, Alphafold-predicted F13L coding for artificially-constructed mutants by pooling some of the most abundant mutations were targeted to offer a simplified prove-of-concept application of DWBEL coevolutions. The initial attempts to co-evolve Tecovirimat-derived ligands were unsuccessful due to the shallow grooves targeted at previously proposed F13L docking surface targets. Apparently, such targets were not capable to generate appropriated cavities for high affinity docking even when increasing computer memories and the number of co-evolution runs. After numerous trial-and-error efforts, an alternative strategy was successfully developed, consisting in: i) Including both highly specific non-toxic filtering during co-evolution together with higher computer memories, ii) Improving 2D structure conservation during the data exchanges between DWBEL / ADV programs by using mmff94s+ force-field conformers (six alternative force-fields altered 2D structures and affinities), and iii) Exploring alternative F13L inner cavities as detected by blind-docking.