# Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant

## TL;DR

The D614G variant of the SARS-CoV-2 Spike protein is more infectious but still responds to antibodies targeting the receptor binding domain.

## Contribution

Demonstrates that the D614G variant increases infectivity without reducing antibody sensitivity.

## Key findings

- D614G is three to nine-fold more infectious than the ancestral form in human and animal cell lines.
- Monoclonal antibodies targeting the receptor binding domain retain full neutralization potency against D614G.
- D614G likely contributed to the rapid global spread of SARS-CoV-2.

## Abstract

The SARS-CoV-2 spike (S) protein variant D614G supplanted the ancestral virus worldwide in a matter of months. Here we show that D614G was more infectious than the ancestral form on human lung cells, colon cells, and cells rendered permissive by ectopic expression of various mammalian ACE2 orthologs. Nonetheless, 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 a critical interprotomer contact and that this dramatically shifts the S protein trimer conformation toward an ACE2-binding and fusion-competent state. Consistent with the more open conformation, neutralization potency of antibodies targeting the S protein receptor-binding domain was not attenuated. These results indicate that D614G adopts conformations that make virion membrane fusion with the target cell membrane more probable but that D614G retains susceptibility to therapies that disrupt interaction of the SARS-CoV-2 S protein with the ACE2 receptor.