Pfam 24.0 (11,912 families) [32] is a high quality resource for domains and families. A valid cross-taxa list was generated. Eukaryotes and viruses cross-taxa resulted in 1,165 Pfam entries. The following filtration steps were applied: (i) Pfam families with at least one viral protein and at least one metazoan protein (taxid: 33208), total of 859 Pfam families. (ii) Restricting the Pfam to families that have at least one metazoan protein and at least one metazoan-infecting virus resulted in 796 Pfam families. (iii) Pfam families with .95% viral proteins for structural element of the virus (e.g., Env, Coat, Capsid). (iv) Enzymes of the replication system were excluded, as these genes are the outcome of several events of genetic exchange [55] . Specifically, we excluded families of RNA/DNA polymerases (39 families), Exo/ Endonuclease (16 families), Helicase (15 families), tRNA synthetase (8 families) and Primase (8 families). We also manually eliminated the cluster represented by the GFP (PF01353) that reflects the inevitable contamination from the extensive use of GFP as vectors in many molecular biology techniques. The filtered list includes 667 protein Pfam families (Supplemental data Table S3 ).