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Cell Entry and Receptor Usage for SARS-CoV-2

The capacity to predict the zoonotic potential of newly detected viruses has been severely hindered by a lack of functional data for these animal virus sequences.

Here, we have developed a rapid and cost-effective platform with which to functionally test large groups of related viruses for zoonotic potential. 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.

Taken together with the latest outbreak of SARS-CoV-2 in humans, these findings underscore the importance of continued surveillance of coronaviruses at the sequence and functional levels in order to better prepare for the next emerging virus.

Letko, M., Marzi, A. & Munster, V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nature Microbiology (2020).

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