In this study, we unexpectedly found that NeoCoV and its close relative, PDF-2180-CoV, can efficiently use some types of bat Angiotensin-converting enzyme 2 (ACE2) and, less favorably, human ACE2 for entry. NeoCoV efficiently infects human ACE2 expressing cells after a T510F mutation on the receptor-binding motif (RBM).
Considering the extensive mutations in the RBD regions of the SARS-CoV-2 variants, especially the heavily mutated Omicron variant, these viruses may hold a latent potential to infect humans through further adaptation via antigenic drift. It is also very likely that their relatives with human emergence potential are circulating somewhere in nature.
