In the absence of drugs approved for ORF8, most probable its best cavities to target could be located at its AB homodimer interface, as already suggested before by targeting the 20 C disulphide bond . Alternatively, here we chose a 45x45x45 Å wide grid surrounding the whole ORF8 homodimer molecule (blind-docking) to search for any other alternative cavities, leaving the docking programs the selection of the best cavities. To start such search, we employed DW-BEL co-evolution because it usually generated tens of thousands of rawchildren from any parent molecule to select thousands of children fitting the supplied cavity (fitted-children). However, to start DW-BEL co-evolutions, not only one parent ligand but also a protein-ligand complex was required to define a flexible target cavity. After preliminary experiments demonstrated the feasibility of using pseudoligands for both of the DW-BEL requirements mentioned above, the so-called erizo pseudoligand was manually designed, optimized by several coevolution iterations, manually drawn in MolSoft and coded into an erizo.sdf file. The optimized erizo pseudoligand was an star-like molecule with a central carbon branched by 4 arms of 7 carbons per arm, all carbons were saturated with methyls to maximize its cavity (Figure up-left). The erizo.sdf file was merged with 7jtl.pdb at PyMol and manually moved to the center of the homodimer interface to "create" an erizo's cavity (Figure , red spheres).