{Reference Type}: Journal Article
{Title}: Molecular basis for receptor recognition and broad host tropism for merbecovirus MjHKU4r-CoV-1.
{Author}: Zhao Z;Li X;Chai Y;Liu Z;Wang Q;Gao GF;
{Journal}: EMBO Rep
{Volume}: 25
{Issue}: 7
{Year}: 2024 Jul 14
{Factor}: 9.071
{DOI}: 10.1038/s44319-024-00169-8
{Abstract}: A novel pangolin-origin MERS-like coronavirus (CoV), MjHKU4r-CoV-1, was recently identified. It is closely related to bat HKU4-CoV, and is infectious in human organs and transgenic mice. MjHKU4r-CoV-1 uses the dipeptidyl peptidase 4 (DPP4 or CD26) receptor for virus entry and has a broad host tropism. However, the molecular mechanism of its receptor binding and determinants of host range are not yet clear. Herein, we determine the structure of the MjHKU4r-CoV-1 spike (S) protein receptor-binding domain (RBD) complexed with human CD26 (hCD26) to reveal the basis for its receptor binding. Measuring binding capacity toward multiple animal receptors for MjHKU4r-CoV-1, mutagenesis analyses, and homology modeling highlight that residue sites 291, 292, 294, 295, 336, and 344 of CD26 are the crucial host range determinants for MjHKU4r-CoV-1. These results broaden our understanding of this potentially high-risk virus and will help us prepare for possible outbreaks in the future.