Cathepsins inhibitor E64d treatment absolutely inhibited the infection of WT, D614G, N501Y.V1 and N501Y.V2 RBD pseudoviruses into 293T-hACE2 cells (Figure 5A and Supplementary Figures S4A, B), indicating that CatB/L is the dominant proteases required for priming of SARS-CoV-2 S protein in TMPRSS2- cells. Here, TMPRSS2 is linked to infection.