The DW-BEL co-evolutions applied in this work have benefit from improvements that have been incorporated step-by-step during the last months to their algorithms targeting different protein / ligand models . However, it seems likely that further explorations into the vast chemical space to search for additional ORF8 ligand alternatives, would demand higher computer memories. In particular, to overcome the steric difficulties of higher affinity insertions into the narrow space between the A and B ORF8 interface, computers with more speed and memories would be required.