While most conventional antiviral drugs target proteins that are virus-encoded, cellular proteins essential for viral replication are currently considered to be alternative potential targets for antiviral therapy [84, 85, 86] . With the exception of Ebola virus, whose glycoprotein cleavage by the proprotein convertase furin is not essential for virus replication in cell culture and virulence in nonhuman primates [71, 87, 88, 89] , maturation cleavage of surface glycoproteins of several virus species by endoproteases is a key determinant for host cell tropism and pathogenicity [90] . Thus, the emergence of viral escape mutants that confer resistance due to targeted inhibition of an endogenous protease is rather unlikely. In S1P-deficient SRD-12B cells, which were persistently infected with Junin virus vaccine strain Candid 1, no virus escape variants possessing a cleavage motif other than a S1P recognition motif have evolved, indicating a low potential of arenaviruses to develop de novo a different glycoprotein maturation pathway [33] . This observation together with our findings that inhibition of S1P significantly affects LASV GP processing and virus infectivity should encourage the development of S1P inhibitors as a potential drug target to counteract infections caused by pathogenic arenaviruses.