PDF(Pubmed)
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.
摘要：
一种新的穿山甲来源的MERS样冠状病毒（CoV），最近发现了MjHKU4r-CoV-1。它与蝙蝠HKU4-CoV密切相关，并且在人体器官和转基因小鼠中具有传染性。MjHKU4r-CoV-1使用二肽基肽酶4（DPP4或CD26）受体进入病毒，并具有广泛的宿主嗜性。然而,其受体结合的分子机制和宿主范围的决定因素尚不清楚。在这里，我们确定了与人CD26（hCD26）复合的MjHKU4r-CoV-1刺突（S）蛋白受体结合域（RBD）的结构，以揭示其受体结合的基础。测量MjHKU4r-CoV-1对多种动物受体的结合能力，诱变分析，和同源性建模强调，CD26的残基位点291、292、294、295、336和344是MjHKU4r-CoV-1的关键宿主范围决定因素。这些结果扩大了我们对这种潜在高风险病毒的理解，并将帮助我们为未来可能的爆发做好准备。
