A new preprint from researchers at Yale and collaborators [Alfajaro et al., 2025] sheds light on how certain bat coronaviruses may cross species boundaries, offering valuable insights for pandemic preparedness. Using Cryo-EM and the Apollo event-based camera, the team investigated the HKU5 strain of bat merbecovirus, a close relative of MERS-CoV.

The study reveals that HKU5 uses the host receptor site ACE2 to enter into bat cells, but also those of American mink and stoats. This suggests these small carnivores could act as intermediate hosts for viral transmission to humans. Importantly, the virus appears to use ACE2 in a structurally distinct way compared to MERS-CoV, meaning that existing MERS-based vaccines and antibodies offer little protection.

As zoonotic spillover remains a persistent threat, studies like this underscore the importance of structural virology in understanding how viruses adapt—and how we can stay ahead of them.

HKU5 bat merbecoviruses use divergent mechanisms to engage bat and mink ACE2 as entry receptors.
M.M. Alfajaro et al. bioRxiv 2025.02.12.637862; doi: https://doi.org/10.1101/2025.02.12.637862

Read the abstract here: https://www.biorxiv.org/content/10.1101/2025.02.12.637862v1.full