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Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses.
Nature Microbiology ( IF 20.5 ) Pub Date : 2020-02-24 , DOI: 10.1038/s41564-020-0688-y
Michael Letko 1 , Andrea Marzi 1 , Vincent Munster 1
Affiliation  

Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.

中文翻译:

SARS-CoV-2 和其他谱系 B β冠状病毒的细胞进入和受体使用的功能评估。

在过去的 20 年里,几种冠状病毒已经跨越物种屏障进入人类,导致严重的、通常是致命的呼吸道疾病的爆发。自从 SARS-CoV 首次在动物市场中被发现以来,全球病毒组学项目已经在不同的动物和地理区域中发现了数千个冠状病毒序列。不幸的是,很少有工具可用于对这些病毒感染人类的​​能力进行功能测试,这严重阻碍了预测下一次人畜共患病毒爆发的努力。在这里,我们开发了一种方法来快速筛选谱系 B β冠状病毒,例如 SARS-CoV 和最近的 SARS-CoV-2,以了解受体的使用及其感染不同物种细胞类型的能力。我们表明,病毒进入过程中的宿主蛋白酶加工是几种 B 系病毒的重要障碍,绕过该障碍允许几种 B 系病毒通过未知受体进入人体细胞。我们还展示了不同谱系 B 病毒如何重组以进入人体细胞,并确认人类 ACE2 是最近出现的 SARS-CoV-2 的受体。
更新日期:2020-02-24
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