Wang Chenghai, Nan Xiaoyan, Deng Yang, Fan Shilong, Li Xin, Lan Jun
School of Biomedical Sciences, Hunan University, Changsha, Hunan, China.
Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs, The Third Hospital of Changsha, Changsha, Hunan, China.
Structure. 2025 Jul 3;33(7):1178-1185.e2. doi: 10.1016/j.str.2025.04.004. Epub 2025 Apr 29.
Bat coronaviruses ZXC21 and ZC45 were discovered before the COVID-19 outbreak and share approximately 86% genome homology with SARS-CoV-2. Earlier studies indicated that ZXC21 and ZC45 may be involved in the emergence of SARS-CoV-2. However, the cell invasion mechanisms of ZXC21 and ZC45 remain unclear. Here, we determined the crystal structure of the ZXC21 receptor-binding domain (RBD) and found that the core structure shared high similarity with SARS-CoV-2, MERS-CoV, human coronavirus (HCoV)-HKU1, SARS-CoV, and HCoV-OC43 RBDs, whereas the receptor-binding motifs (RBMs) differ. We demonstrated that the ZXC21 RBD had no interaction with the human coronavirus receptors angiotensin-converting enzyme 2 (ACE2), dipeptidylpeptidase 4 (DPP4), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2) by surface plasmon resonance (SPR). Moreover, the P5S-3B11 Fab can bind to the ZXC21 RBD, indicating that this SARS-CoV-2 core-targeting antibody may retain neutralizing activity toward the ZXC21 coronavirus. Our results revealed the bat coronavirus ZXC21 RBD structure, which may provide further insights into the evolution of SARS-CoV-2 and the other human beta-coronaviruses.
蝙蝠冠状病毒ZXC21和ZC45在新冠疫情爆发前就已被发现，与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的基因组同源性约为86%。早期研究表明，ZXC21和ZC45可能与SARS-CoV-2的出现有关。然而，ZXC21和ZC45的细胞入侵机制仍不清楚。在此，我们确定了ZXC21受体结合域（RBD）的晶体结构，发现其核心结构与SARS-CoV-2、中东呼吸综合征冠状病毒（MERS-CoV）、人冠状病毒（HCoV）-HKU1、SARS-CoV和HCoV-OC43的RBD具有高度相似性，而受体结合基序（RBM）不同。我们通过表面等离子体共振（SPR）证明，ZXC21 RBD与人冠状病毒受体血管紧张素转换酶2（ACE2）、二肽基肽酶4（DPP4）、氨肽酶N（APN）或跨膜丝氨酸蛋白酶2（TMPRSS2）没有相互作用。此外，P5S-3B11 Fab可以结合ZXC21 RBD，表明这种靶向SARS-CoV-2核心的抗体可能对ZXC21冠状病毒保持中和活性。我们的结果揭示了蝙蝠冠状病毒ZXC21 RBD的结构，这可能为深入了解SARS-CoV-2和其他人类β冠状病毒的进化提供进一步的线索。
