Functional assessment of cell entry and receptor use for merbecoviruses

The merbecovirus subgenus of coronaviruses includes Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which is a zoonotic respiratory pathogen that transmits from dromedary camels to humans and causes severe respiratory disease. Viral discovery efforts have uncovered hundreds of merbecoviruses in different species across multiple continents, but few of these viruses have been isolated or studied under laboratory conditions, leaving basic questions regarding their threat to humans unresolved. Viral entry into host cells is considered an early and critical step for transmission between hosts. In this study, a scalable approach to assessing novel merbecovirus cell entry was developed and used to measure receptor use across the entire merbecovirus subgenus. Merbecoviruses are sorted into four clades based on the receptor binding domain of the spike glycoprotein. Receptor tropism is clade-specific, with only one clade using DPP4 and multiple clades using ACE2, including the entire HKU5 cluster of bat coronaviruses.