Cell 181, 894–904 (2020)
Cell 181, 281–292 (2020)
On the basis of sequence information and knowledge of the cellular entry route of other coronaviruses, the host protein angiotensin-converting enzyme 2 (ACE2) was a prime candidate for the binding partner of the SARS-CoV-2 spike protein to enable viral entry.
Walls et al. showed that this spike protein enables SARS-CoV-2 to infect ACE2-expressing cells in vitro, and described a novel enzymatic cleavage site in the SARS-CoV-2 spike protein, which the authors propose may diversify the virus’ tissue tropism. The crystal structure of the C-terminal domain of SARS-CoV-2 spike protein bound to human ACE2 generated by Wang et al. predicts that the SARS-CoV-2 spike protein binds its target with greater affinity than that of its relative, SARS-CoV.
The two studies support the development of therapeutic and immunological strategies that target the viral spike protein’s ACE2-binding domains, and ACE2 expression in human tissues may explain both pulmonary viral tropism and extrapulmonary viral tropism.
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Carvalho, T. ACE2, the viral gateway. Nat Med 26, 1807 (2020). https://doi.org/10.1038/s41591-020-01166-9