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

BioRxiv : the Preprint Server for Biology
L. YurkovetskiyJeremy Luban

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.

Citations

Sep 10, 2020·Nature·Ewen Callaway
Dec 22, 2020·International Journal of Antimicrobial Agents·Ádám NagyBalázs Győrffy
Nov 15, 2020·Viruses·Lin Wang, Ye Xiang
Feb 18, 2021·Critical Reviews in Clinical Laboratory Sciences·Parham HabibzadehMohammad Ali Faghihi
Dec 18, 2020·ACS Pharmacology & Translational Science·Kirill GorshkovWei Zheng

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Datasets Mentioned

BETA
EMD-22301

Methods Mentioned

BETA
transfection
flow cytometry
GISAID
transfections
surface
chip

Clinical Trials Mentioned

NCT04425629
NCT04426695

Software Mentioned

GISAID
Scrubber
biopython
sites
Nextstrain
SnpEff
PHENIX
MAFFT
bcftools
FlowJo

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