Cell
Volume 183, Issue 3, 29 October 2020, Pages 739-751.e8
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Article
Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant

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Highlights

  • The SARS-CoV-2 D614G S protein variant supplanted the ancestral virus in people

  • D614G increases infectivity on human lung cells or cells with bat or pangolin ACE2

  • D614G is potently neutralized by antibodies targeting the receptor-binding domain

  • D614G shifts S protein conformation toward an ACE2-binding fusion-competent state

Summary

The SARS-CoV-2 spike (S) protein variant D614G supplanted the ancestral virus worldwide, reaching near fixation in a matter of months. Here we show that D614G was more infectious than the ancestral form on human lung cells, colon cells, and on cells rendered permissive by ectopic expression of human ACE2 or of ACE2 orthologs from various mammals, including Chinese rufous horseshoe bat and Malayan pangolin. D614G did not alter S protein synthesis, processing, or incorporation into SARS-CoV-2 particles, but D614G affinity for ACE2 was reduced due to a faster dissociation rate. Assessment of the S protein trimer by cryo-electron microscopy showed that D614G disrupts an interprotomer contact and that the conformation is shifted toward an ACE2 binding-competent state, which is modeled to be on pathway for virion membrane fusion with target cells. Consistent with this more open conformation, neutralization potency of antibodies targeting the S protein receptor-binding domain was not attenuated.

Keywords

SARS-CoV-2
COVID-19
coronavirus
Spike protein
ACE2
pandemic
cryo-electron microscopy
neutralizing antibody
infectivity

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12

These authors contributed equally

13

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