The RBD is an immunodominant antibody target in natural infection [10] and highly potent NAbs directed to the RBD can block infection by binding to the ACE2 receptor-binding motif (RBM) and directly blocking ACE2 binding, via steric blockade of ACE2 binding, by locking RBDs in the down orientation to preclude ACE2 binding, or by triggering premature refolding of S1-S2 into the post-fusion state with shedding of S1 [11–18]. Here, ACE2 is linked to infection.