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

Cell
L. YurkovetskiyJeremy Luban

Abstract

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.

References

Nov 11, 1999·Journal of Molecular Recognition : JMR·D G Myszka
Apr 12, 2003·The New England Journal of Medicine·Christian DrostenHans Wilhelm Doerr
Apr 12, 2003·The New England Journal of Medicine·Thomas G KsiazekUNKNOWN SARS Working Group
Dec 9, 2003·Trends in Microbiology·Edward C Holmes
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Oct 19, 2011·PLoS Pathogens·Gretja SchnellRonald Swanstrom
Oct 19, 2012·The New England Journal of Medicine·Ali M ZakiRon A M Fouchier
Jan 19, 2013·Molecular Biology and Evolution·Kazutaka Katoh, Daron M Standley
Nov 3, 2014·Annual Review of Virology·Everett Clinton SmithMark R Denison
Nov 5, 2016·Cell·Richard A UrbanowiczJonathan K Ball
Feb 28, 2017·Cell Host & Microbe·May K WangJames M Cunningham
Apr 7, 2017·Euro Surveillance : Bulletin Européen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin·Yuelong Shu, John McCauley
Aug 16, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jesper PallesenJason S McLellan
May 24, 2018·Bioinformatics·James HadfieldRichard A Neher
Nov 2, 2018·PLoS Pathogens·Amir SaberiAlexander E Gorbalenya
Sep 17, 2019·Advances in Virus Research·M Alejandra Tortorici, David Veesler
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Feb 20, 2020·Nature Microbiology·Nathan D GrubaughEdward C Holmes
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Mar 4, 2020·Nature Microbiology·UNKNOWN Coronaviridae Study Group of the International Committee on Taxonomy of Viruses
Mar 11, 2020·Cell·Alexandra C WallsDavid Veesler
Mar 29, 2020·Nature·Tommy Tsan-Yuk LamWu-Chun Cao
Apr 1, 2020·Nature·Jian ShangFang Li
Apr 15, 2020·Nature Medicine·Kristian G AndersenRobert F Garry

❮ Previous
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Citations

Oct 31, 2020·Wiener klinische Wochenschrift·Franz X Heinz, Karin Stiasny
Nov 27, 2020·Nature Communications·Lucy van DorpFrançois Balloux
Oct 28, 2020·Nature·Jessica A PlantePei-Yong Shi
Jan 8, 2021·Cell·Wilfredo F Garcia-BeltranAlejandro B Balazs
Jan 7, 2021·Trends in Genetics : TIG·Yang ZhangMario Juhas
Jan 6, 2021·Immunology Letters·Adnan Erol
Dec 12, 2020·Cell Host & Microbe·Drew WeissmanDavid C Montefiori
Dec 12, 2020·Emerging Microbes & Infections·Victoria ElizondoRalf Duerr
Jan 19, 2021·Indian Journal of Medical Microbiology·Biswajyoti Borkakoty, Nargis K Bali
Dec 15, 2020·Journal of Virology·Hanh T NguyenJoseph Sodroski
Feb 12, 2021·JAMA : the Journal of the American Medical Association·John R MascolaAnthony S Fauci
Feb 14, 2021·Science Advances·Carolina Beltrán-PavezRicardo Soto-Rifo
Feb 14, 2021·Proceedings of the National Academy of Sciences of the United States of America·Donald J BentonSteven J Gamblin
Dec 29, 2020·Human Genomics·Giuseppe NovelliJuergen K V Reichardt
Nov 20, 2020·Nature·James Zengel, Jan E Carette
Feb 8, 2021·Stem Cell Research·Gangyu SunZhizhi Wang
Nov 4, 2020·Cell Research·Imre Berger, Christiane Schaffitzel
Jan 13, 2021·Signal Transduction and Targeted Therapy·Anshumali Mittal, Vikash Verma
Jan 19, 2021·Current Genetic Medicine Reports·Phoebe EllisGary R McLean
Feb 2, 2021·Molecular Therapy. Methods & Clinical Development·Xinping FuXiaoliu Zhang
Feb 16, 2021·Science China. Life Sciences·Aria C Shi, Xuping Xie
Nov 18, 2020·Biochemical and Biophysical Research Communications·Danielle C GrovesAdrienn Angyal
Nov 23, 2020·Biochemical and Biophysical Research Communications·Cody B JacksonHyeryun Choe
Oct 19, 2020·Biochemical and Biophysical Research Communications·Meng YuanIan A Wilson
Nov 26, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Girish PathangeyAmr E Abbas
Mar 6, 2021·Emerging Microbes & Infections·Kelvin Kai-Wang ToKwok-Yung Yuen
Mar 3, 2021·Signal Transduction and Targeted Therapy·Kathleen D Engelman, Alan N Engelman
Mar 3, 2021·Signal Transduction and Targeted Therapy·Prerna AroraMarkus Hoffmann
Feb 27, 2021·Briefings in Bioinformatics·Jim Warwicker

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Datasets Mentioned

BETA
EMD-22301

Methods Mentioned

BETA
flow cytometry
transfection
electron cryotomography
transfections
surface
chip

Clinical Trials Mentioned

NCT04425629
NCT04426695

Software Mentioned

sites
Biacore T200 Evaluation
GraphPad
Relion3
FlowJo
mafft
matplotlib
SnpEff
bcftools
Prism

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