Similarly, based on cryo-EM analyses, it has been suggested that alterations of Q493R, G496S, and Q498R in the RBD of the Omicron S form may allow the formation of stronger interactions with ACE2 that compensate for the disruptive effect of K417N (Mannar et al., 2021), but none of these four mutations individually significantly affected S-mediated infection (Figure 2). Here, ACE2 is linked to infection.