Indeed, at 4 h post infection, SARS-CoV-2 S partially colocalized with AXL and host endocytosis and vesicle trafficking markers inside cells, including Caveolin1 (CAV1), Early endosome antigen 1 (EEA1), DCC-interacting protein 13-alpha (APPL1), Clathrin heavy chain 1 (CLTC) and Syntaxin-6 (STX6) (Fig. 4g), while knocking out AXL in H1299 cells blocked the colocalization between S and host endocytosis and vesicle trafficking markers (Supplementary information, Fig. S5c), indicating that SARS-CoV-2 is internalized and penetrates early endosomes in a clathrin-dependent manner after it binds AXL. Here, APPL1 is linked to infection.