The use of co-crystal structures to identify ubiquitin and ISG15 interacting regions and subsequent re-engineering of enzymatic activity has also been applied to the study of cellular DUBs such as USP21, and to another class of viral proteases that also have DUB activity such as the ovarian tumor (OTU) domains of Crimean Congo Hemorrhagic Fever Virus (CCHFV) [14], [15], [16]. This evidence concerns the gene USP21 and ovarian neoplasm.