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

report the circulation of a novel MERS-like coronavirus in Malayan pangolins, named Manis javanica HKU4-relatedcoronavirus (MjHKU4r-CoV). Among 86 animals, four tested positive by pan-CoV PCR, and seven tested seropositive (11 and12.8%). Four nearly identical (99.9%) genome sequences were obtained, and one virus was isolated (MjHKU4r-CoV-1). Thisvirus utilizes human dipeptidyl peptidase-4 (hDPP4) as a receptor and host proteases for cell infection, which is enhanced by afurin cleavage site that is absent in all known bat HKU4r-CoVs. The MjHKU4r-CoV-1 spike shows higher binding affinity forhDPP4, and MjHKU4r-CoV-1 has a wider host range than bat HKU4-CoV. MjHKU4r-CoV-1 is infectious and pathogenic inhuman airways and intestinal organs and in hDPP4-transgenic mice. Our study highlights the importance of pangolins as reservoirhosts of coronaviruses poised for human disease emergence.