Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State

View ORCID ProfileRachael A. Mansbach, View ORCID ProfileSrirupa Chakraborty, View ORCID ProfileKien Nguyen, View ORCID ProfileDavid C. Montefiori, View ORCID ProfileBette Korber, View ORCID ProfileS. Gnanakaran
doi: https://doi.org/10.1101/2020.07.26.219741
Rachael A. Mansbach
1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rachael A. Mansbach
Srirupa Chakraborty
1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545
2Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Srirupa Chakraborty
Kien Nguyen
1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kien Nguyen
David C. Montefiori
3Duke Human Vaccine Institute & Department of Surgery, Durham, NC 27710
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David C. Montefiori
Bette Korber
1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Bette Korber
S. Gnanakaran
1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for S. Gnanakaran
  • For correspondence: gnana@lanl.gov
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Summary

The COVID-19 pandemic underwent a rapid transition with the emergence of a SARS-CoV-2 variant that carried the amino acid substitution D614G in the Spike protein that became globally prevalent. The G-form is both more infectious in vitro and associated with increased viral loads in infected people. To gain insight into the mechanism underlying these distinctive characteristics, we employed multiple replicas of microsecond all-atom simulations to probe the molecular-level impact of this substitution on Spike’s closed and open states. The open state enables Spike interactions with its human cellular receptor, ACE2. Here we show that changes in the inter-protomer energetics due to the D614G substitution favor a higher population of infection-capable (open) states. The inter-protomer interactions between S1 and S2 subunits in the open state of the D-form are asymmetric. This asymmetry is resolved in the G-form due to the release of tensile hydrogen bonds resulting in an increased population of open conformations. Thus, the increased infectivity of the G-form is likely due to a higher rate of profitable binding encounters with the host receptor. It is also predicted to be more neutralization sensitive due to enhanced exposure of the receptor binding domain, a key target region for neutralizing antibodies.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted July 26, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State
Rachael A. Mansbach, Srirupa Chakraborty, Kien Nguyen, David C. Montefiori, Bette Korber, S. Gnanakaran
bioRxiv 2020.07.26.219741; doi: https://doi.org/10.1101/2020.07.26.219741
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
The SARS-CoV-2 Spike Variant D614G Favors an Open Conformational State
Rachael A. Mansbach, Srirupa Chakraborty, Kien Nguyen, David C. Montefiori, Bette Korber, S. Gnanakaran
bioRxiv 2020.07.26.219741; doi: https://doi.org/10.1101/2020.07.26.219741

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biophysics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4655)
  • Biochemistry (10307)
  • Bioengineering (7618)
  • Bioinformatics (26203)
  • Biophysics (13453)
  • Cancer Biology (10625)
  • Cell Biology (15348)
  • Clinical Trials (138)
  • Developmental Biology (8456)
  • Ecology (12761)
  • Epidemiology (2067)
  • Evolutionary Biology (16777)
  • Genetics (11361)
  • Genomics (15407)
  • Immunology (10556)
  • Microbiology (25060)
  • Molecular Biology (10162)
  • Neuroscience (54128)
  • Paleontology (398)
  • Pathology (1655)
  • Pharmacology and Toxicology (2877)
  • Physiology (4315)
  • Plant Biology (9204)
  • Scientific Communication and Education (1582)
  • Synthetic Biology (2543)
  • Systems Biology (6753)
  • Zoology (1453)