心鼻蝙蝠冠状病毒利用人类CEACAM6进入细胞,这一成果由皮尔布赖特研究所Dalan Bailey研究组经过不懈努力而取得。2026年4月22日出版的《自然》杂志发表了这项成果。
在这里,该课题组研究人员选择了一种保留最大系统发育多样性的计算方法,选择了一个最佳的α冠状病毒刺突蛋白子集来筛选广泛的冠状病毒受体文库。大多数选择的刺突蛋白没有使任何已建立的冠状病毒受体成为主题。
而心鼻蝙蝠冠状病毒KY43 (CcCoV-KY43)假型刺突蛋白可以进入人细胞。利用重组CcCoV受体结合域(RBD)和人类受体筛选平台,该课题组鉴定了与人类CEACAM蛋白CEACAM3、CEACAM5和CEACAM6的直接相互作用。人CEACAM6 -一种在人肺中广泛表达的蛋白的过度表达赋予了对其他难愈的人细胞的容受性。晶体结构表明RBD结合人CEACAM6的氨基末端IgV样结构域。对发现CcCoV-KY43的肯尼亚Taveta地区个体的血清进行免疫监测研究,未显示近期发生外溢的重要证据。对与CcCoV-KY43相关的冠状病毒主题的更广泛表征表明,人类CEACAM6是由在肯尼亚收集的另外两种CcCoVs为主题的。
此外,从中国和中国的鼻鼻蝙蝠分离的病毒主题具有更有限的非人类CEACAM6趋向性。它们,以CEACAM6为主题的冠状病毒主题可能在地理上广泛分布,而来自东非的病毒主题显示出传播给人类的潜力。
据了解,根据病毒进入人类细胞的能力确定具有人畜共患潜力的病毒主题,是大流行预测、预防和防备的关键组成部分。
附:英文原文
Title: Heart-nosed bat alphacoronaviruses use human CEACAM6 to enter cells
Author: Gallo, Giulia, Di Nardo, Antonello, Lugano, Doreen, Roberts, Adam J., Kutima, Bernadette Ataku, Okombo, Moses, Dewantari, Aghnianditya Kresno, Buckley, Florence M. M., Wright, Gavin J., Nyagwange, James, Agwanda, Bernard, Graham, Stephen C., Bailey, Dalan
Issue&Volume: 2026-04-22
Abstract: Identifying viruses with zoonotic potential on the basis of their ability to enter human cells is a critical component of pandemic prediction, prevention and preparedness. Here using a computational approach that retains maximum phylogenetic diversity, we selected an optimal subset of alphacoronavirus spike proteins to screen against broad coronavirus receptor libraries. Most of the selected spike proteins did not use any of the established coronavirus receptors. However, the pseudotyped spike protein of Cardioderma cor (heart-nosed bat) coronavirus KY43 (CcCoV-KY43) could enter human cells. Using a recombinant CcCoV receptor-binding domain (RBD) and a human receptor screening platform, we identified direct interactions with the human CEACAM proteins CEACAM3, CEACAM5 and CEACAM6. Overexpression of human CEACAM6—a protein widely expressed in the human lung—conferred permissivity to otherwise refractory human cells. A crystal structure showed that the RBD binds the amino-terminal IgV-like domain of human CEACAM6. Immune surveillance studies using sera of individuals from the Taveta region of Kenya, where CcCoV-KY43 was identified, did not show significant evidence of recent spillover. Wider characterization of alphacoronaviruses related to CcCoV-KY43 showed that human CEACAM6 is used by two other CcCoVs collected in Kenya. Moreover, there was more restricted nonhuman CEACAM6 tropism for viruses isolated from Rhinolophus bats from Russia and China. Thus, alphacoronaviruses that use CEACAM6 are probably geographically widespread, and viruses from East Africa show potential for transmission to humans.
DOI: 10.1038/s41586-026-10394-x
Source: https://www.nature.com/articles/s41586-026-10394-x
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html
