As shown in Fig 5D, Y498Q substitution in RaTG13 S protein showed a significant reduction in transduction on 293/hACE2 cells and almost abolished infection on all RaACE2 variants, consistent with our previous reports that Q might be favored over Y at position 498 of RaTG13 S protein in interaction with various ACE2 [18]. Here, ACE2 is linked to infection.