SARS-CoV-2 and SARS-CoV differ in their cell tropism and drug sensitivity profiles

Denisa Bojkova; Jake E. McGreig; Katie-May McLaughlin; Stuart G. Masterson; Marek Widera; Verena Krähling; Sandra Ciesek; Mark N. Wass; Martin Michaelis; Jindrich Cinatl

concentrations. Moreover, although both compounds inhibited SARS-CoV-2-induced 309 CPE formation, they displayed limited effects on the SARS-CoV-2 replication cycle as 310 indicated by high levels of double-stranded RNA in both nafamostat-and camostat-311 treated SARS-CoV-2-infected cells ( Figure 4B ). Hence, both camostat and nafamostat 312 may primarily exert cytoprotective effects in SARS-CoV-2-infected cells, which inhibit 313 syncytium formation and cell lysis, but may not inhibit SARS-CoV-2 replication in the 314 same way. 315 aprotinin was also more effective against SARS-CoV-2-induced CPE formation (IC50 329 22.9 KIU/mL) than against SARS-CoV (IC50 118 KIU/mL) ( Figure 4A ). In addition and 330 in contrast to nafamostat and camostat, aprotinin also inhibited double-stranded RNA 331 formation in SARS-CoV-2-infected cells ( Figure 4B ). Therapeutic aprotinin plasma 332 levels were described to reach 147 ± 61 KIU/mL after the administration of 1,000,000 333