Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses.
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TLDR
An approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recently emerged SARS -CoV-2, for receptor usage and their ability to infect cell types from different species is developed.Abstract:
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. This study describes the development of an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recently emerged SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. Using it, they confirm human ACE2 as the receptor for SARs-CoV-2 and show that host protease processing during viral entry is a significant barrier for viral entry.read more
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Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.
Alexandra C. Walls,Young-Jun Park,M. Alejandra Tortorici,M. Alejandra Tortorici,Abigail Wall,Andrew T. McGuire,Andrew T. McGuire,David Veesler +7 more
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Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.
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TL;DR: High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.
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The proximal origin of SARS-CoV-2.
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TL;DR: This study determines the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2 and sheds light on the structural features that increase its binding affinity to ACE2.
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