Apart from the hypothetical pseudoligand trick used here to start coevolutions, other limitations may also include the explorations using fixed dockingcavity geometries. Considering the possible influences of amino acid side-chain mobilities on the ORF8 docking affinity estimations, those mobilities may add small variations to best accommodate any of the predicted ligands or new ones. However, their higher memory demands would made the explorations of such possibilities difficult to apply to the high numbers of grandchildren molecules identified here. Alternatively, other more adaptable or flexible docking cavities may still exist on ORF8 such as those in: i) the interface of the hypervariable loop A with another ORF8 monomer, such as it was earlier suggested by their surface complementarity identified in crystallographic models with another ORF8 monomer or with ii) the interfaces with some of the many protein molecular surfaces of human proteins with already demonstrated interactions with ORF8 and/or those that have been computationally predicted by interactome studies. Further computational work could further extent these hypothetical alternatives. The 46808 and 16153 erizo's children were co-evolved to generated fitted grandchildren. Grandchildren 16153 were generated by increasing the number of consecutive runs. XXX, same scaffold than the corresponding top-grandchild (green letters).