Beyond ACE2 affinity modulation, the evidence pointing to the utilization of alternative receptors, such as neuropilin-1 and heparan sulfate, to facilitate infection by SARS-CoV-2 highlights the urgent need for surveillance of S protein evolution and the development of broadly neutralizing antibodies targeting conserved viral epitopes to mitigate the risk of immune escape and receptor switching. This evidence concerns the gene ACE2 and infection.