Our temporal analyses revealed that at later infection stages (36–48 hours post-infection [hpi]), SARS-CoV-2 exploits TGF-β-induced lysosomal membrane permeabilization (LMP) and apoptosis for viral release—processes effectively inhibited by SB431542 through suppression of GADD45b and BAX expression. This evidence concerns the gene TGFB1 and infection.