A bat MERS-like coronavirus circulates in pangolins and utilizes human DPP4 and host proteases for cell entry

Cell. 2023 Feb 16;186(4):850-863.e16. doi: 10.1016/j.cell.2023.01.019.


It is unknown whether pangolins, the most trafficked mammals, play a role in the zoonotic transmission of bat coronaviruses. We report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-related coronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and 12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). This virus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by a furin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity for hDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic in human airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoir hosts of coronaviruses poised for human disease emergence.

Keywords: bat MERS-like coronavirus; dipeptidyl peptidase-4; furin cleavage site; pangolin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chiroptera
  • Coronavirus Infections* / veterinary
  • Coronavirus Infections* / virology
  • Coronavirus* / physiology
  • Dipeptidyl Peptidase 4* / genetics
  • Dipeptidyl Peptidase 4* / metabolism
  • Endopeptidases / metabolism
  • Humans
  • Mice
  • Middle East Respiratory Syndrome Coronavirus / genetics
  • Middle East Respiratory Syndrome Coronavirus / metabolism
  • Pangolins*
  • Peptide Hydrolases / metabolism
  • Receptors, Virus / metabolism
  • Virus Internalization


  • Dipeptidyl Peptidase 4
  • DPP4 protein, human
  • Endopeptidases
  • Peptide Hydrolases
  • Receptors, Virus