The metalloproteinase-dependent viral entry pathway is cell type dependent. The effects of drugs on the entry of SARS-CoV-2 S-bearing vesicular stomatitis virus (VSV) pseudotype virus produced by 293T cells are shown. The relative pseudovirus entry was calculated by normalizing the FL activity for each condition to the FL activity of cells infected with SARS-CoV-2 S-bearing pseudovirus in the presence of DMSO alone, which was set to 100%. Values are means ± SD (n = 3/group). *, P < 0.05; **, P < 0.01. Cont, control (cells infected with pseudovirus without S protein); SARS-CoV-2, cells infected with SARS-CoV-2 S-bearing pseudovirus; E-64d, 25 μM E-64d; nafamo, 10 μM nafamostat; marima, 1 μM marimastat. (a) Effects of marimastat, E-64d, and nafamostat on pseudovirus entry in A704, OVISE, and Calu-3 cells, respectively. (b to e) Effects of a single drug treatment or a combination treatment on pseudovirus entry in VeroE6, HEC50B, OVTOKO, and A704 cells (b), IGROV1, OUMS-23, and OVISE cells (c), Calu-3 and Caco-2 cells (d), and HEC50B-TMPRSS2 cells (e).