近日，美国华盛顿大学教授David Veesler及其团队的研究发现FCoV-23刺突蛋白结构域0的缺失增强融合活性与进入动力学。该项研究成果发表在2025年7月9日出版的《自然》上。

在这里，研究组报告了两种FCoV-23尖峰异构体的低温电镜结构，这些异构体对应于宿主内结构域丢失在临床样品中观察到0。失去领地0显著增强进入细胞的致热性和动力学，并可能导致生物型转换和致死性。该研究团队发现FCoV-23可以靶向几种氨基肽酶N同源物作为受体，并揭示受体物种趋向性的分子决定因素，包括调节人类受体接合的聚糖。研究人员确定了感染人类和其他哺乳动物物种的甲型冠状病毒主题之间的抗原关系，并鉴定了一种抑制FCoV-23进入的交叉反应性甲型冠状病毒单克隆抗体。他们的研究结果为开发针对这种高致病性病毒的疫苗和疗法铺平了道路。

据了解，冠状病毒重组和跨越物种屏障的能力影响全球人类和动物健康，并构成大流行威胁。FCoV-23是最近出现的一种高致病性重组冠状病毒，是猫科动物感染性腹膜炎大范围暴发的原因。

附：英文原文

Title: Loss of FCoV-23 spike domain 0 enhances fusogenicity and entry kinetics

Author: Tortorici, M. Alejandra, Choi, Annette, Gibson, Cecily A., Lee, Jimin, Brown, Jack T., Stewart, Cameron, Joshi, Anshu, Harari, Sheri, Willoughby, Isabelle, Treichel, Catherine, Leaf, Elizabeth M., Bloom, Jesse D., King, Neil P., Tait-Burkard, Christine, Whittaker, Gary R., Veesler, David

Issue&Volume: 2025-07-09

Abstract: The ability of coronaviruses to recombine and cross species barriers affects human and animal health globally and is a pandemic threat1,2. FCoV-23 is a recently emerged, highly pathogenic recombinant coronavirus responsible for a widespread outbreak of feline infectious peritonitis. Here we report cryogenic electron microscopy structures of two FCoV-23 spike isoforms that correspond to the in-host loss of domain0 observed in clinical samples. The loss of domain0 markedly enhances the fusogenicity and kinetics of entry into cells and possibly enables biotype switching and lethality. We show that FCoV-23 can use several aminopeptidaseN orthologues as receptors and reveal the molecular determinants of receptor species tropism, including a glycan that modulates human receptor engagement. We define antigenic relationships among alphacoronaviruses that infect humans and other mammalian species and identify a cross-reactive alphacoronavirus monoclonal antibody that inhibits FCoV-23 entry. Our results pave the way for the development of vaccines and therapeutics that target this highly pathogenic virus.

DOI: 10.1038/s41586-025-09155-z

Source: https://www.nature.com/articles/s41586-025-09155-z