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ACE2, the viral gateway

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.

Credit: Radoslav Zilinsky / Moment / Getty

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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Correspondence to Thiago Carvalho.

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Carvalho, T. ACE2, the viral gateway. Nat Med 26, 1807 (2020).

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