Human site-1 protease (S1P, MEROPS S08.8063), also widely known as subtilisin/kexin-isozyme-1 (SKI-1), is a membranebound subtilisin-related serine endoprotease that belongs to a group of nine mammalian proprotein convertases (PCs) in family S08 [44] [45] [46] . SKI-1/S1P displays unique substrate specificity among the PC members by showing preferred cleavage after non-basic amino acids [47] . SKI-1/S1P cleaves at the carboxyterminus of the peptidyl sequence Arg/Lys-Xaa 3 -Xaa 2 -Leu/ Ser/Thr [48] , where Xaa 3 is any amino acid except Cys at the P3 position of the scissile peptide bond and Xaa 2 is a hydrophobic amino acid containing an alkyl side chain at the P2 position [49] . In addition to the proteolytic processing of transcription factors [36] , SKI-1/S1P participates in the proteolytic activation of viral-envelope glycoproteins of the Lassa virus [50] , the lymphocytic choriomeningitis virus [51] , and the Crimean Congo hemorrhagic fever virus [52] . Importantly, endoproteolytic processing of these viral glycoproteins by SKI-1/S1P is a critical step for the production of infectious progeny viruses, suggesting that SKI-1/S1P may represent an attractive target for therapeutic intervention against human pathogenic arenaviruses [47, 48, [50] [51] [52] .