In recent years improvements were made in the application of bioengineered serpins to combat bacterial and viral infections [39, 72] . For example, the addition of exogenous a 1 -AT-PDX, a potent and selective furin inhibitor, was found to efficiently block human cytomegalovirus infection [39] . However, in contrast to furin, which is known to recycle between the plasma membrane and the TGN via endosomal compartments, membrane-bound S1P is localized in the secretory pathway and can be sorted to endosomal compartments but not to the cell surface [73, 74, 75] . Follow-up studies with small synthetic peptides, which are derived from S1P-specific a 1 -antitrypsins described in the present work, are currently in progress and will address cellular delivery and organelle specific targeting, as well as their inhibitory potential on authentic LASV replication. In analogy to inhibition strategies of the eukaryotic subtilase furin, we previously designed and developed a cell-permeable peptidyl chloromethylketone S1P inhibitor, which contained the LASV GP-C cleavage site, designated dec-RRLL-cmk [76, 77, 78] . This irreversible inhibitor efficiently blocked the processing of LASV GP at nanomolar concentrations, however, because of cell type-dependent toxicity observed by us and others, its potential in vitro use requires further investigation [79, 80] .