In vitro and in vivo characterization of a #bat #merbecovirus with #ACE2- and #DPP4-independent cell entry
ABSTRACT Betacoronaviruses, which have caused three human outbreaks within the last two decades, are thought to originate from bats , raising the concern that bat coronaviruses could cause a novel human outbreak in the future. To determine whether the bat merbecovirus EjCoV-3 strain , previously detected in Eptesicus japonensis in Japan , has the potential to infect humans, we analyzed its cellular entry mechanism. Cellular entry of EjCoV-3 via the spike protein requires protease treatment and is mediated by an unknown receptor, other than DPP4 or ACE2 . We generated cultivable recombinant EjCoV-3 using bacterial artificial chromosome-based reverse genetics and found that it efficiently replicated in human respiratory and intestinal cell cultures as well as nasal ciliated epithelium in hamsters. These findings suggest that bat merbecovirus with ACE2- and DPP4-independent cell entry has the potential to cause human infections , highlighting the importance of extensive bat surveillance f...