The lack of observed ACE2-dependent enhancement to infection by clade 2 and clade 3 sarbecovirus spike proteins, such as YN2013 or BM48–31, can be explained in 3 ways: (1) these RBDs have weak but functionally relevant affinity for ACE2, below the limit of detection of commonly used assay; (2) these RBDs have affinity for certain orthologs of ACE2, but little or no affinity for human ACE2 or for any orthologs that have been tested so far; or (3) these RBDs primarily utilize an entry mechanism distinct from ACE2. Here, ACE2 is linked to infection.