Evidence map›Paper›PMID 32577644›Full record

ArticlebioRxiv : the preprint server for biology2020

Beyond Shielding: The Roles of Glycans in SARS-CoV-2 Spike Protein.

Lorenzo Casalino, Zied Gaieb, Jory A Goldsmith, Christy K Hjorth, Abigail C Dommer, Aoife M Harbison, Carl A Fogarty, Emilia P Barros, Bryn C Taylor, Jason S McLellan and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Lorenzo CasalinoDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Zied GaiebDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Jory A GoldsmithDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Christy K HjorthDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Abigail C DommerDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Aoife M HarbisonDepartment of Chemistry and Hamilton Institute, Maynooth University, Dublin, Ireland.
Carl A FogartyDepartment of Chemistry and Hamilton Institute, Maynooth University, Dublin, Ireland.
Emilia P BarrosDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Bryn C TaylorDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Jason S McLellanDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.
Elisa FaddaDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
Rommie E AmaroDepartment of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.

Funding

Structure, Function and Antigenicity of Coronavirus Spike ProteinsR01AI127521 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI MCLELLAN, JASON SCOTT, WARD, ANDREW BARRETT · 2017 to 2021
$3.1M
A MULTISCALE APPROACH TO TARGET THE ACHILLES HEEL OF P53 CANCER MUTANTS (Equipment Supplement)R01GM132826 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AMARO, ROMMIE E · 2019 to 2022
$1.3M
NIAID NIH HHS R01 AI127521NIGMS NIH HHS R01 GM132826
6 · The paper itself

Abstract

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 15,000,000 infections and 600,000 deaths worldwide to date. Antibody development efforts mainly revolve around the extensively glycosylated SARS-CoV-2 spike (S) protein, which mediates the host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2). Similar to many other viruses, the SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response. Here, we built a full-length model of glycosylated SARS-CoV-2 S protein, both in the open and closed states, augmenting the available structural and biological data. Multiple microsecond-long, all-atom molecular dynamics simulations were used to provide an atomistic perspective on the roles of glycans, and the protein structure and dynamics. We reveal an essential structural role of N-glycans at sites N165 and N234 in modulating the conformational dynamics of the spike's receptor binding domain (RBD), which is responsible for ACE2 recognition. This finding is corroborated by biolayer interferometry experiments, which show that deletion of these glycans through N165A and N234A mutations significantly reduces binding to ACE2 as a result of the RBD conformational shift towards the "down" state. Additionally, end-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of SARS-CoV-2 S protein, which may be exploited by therapeutic efforts targeting this molecular machine. Overall, this work presents hitherto unseen functional and structural insights into the SARS-CoV-2 S protein and its glycan coat, providing a strategy to control the conformational plasticity of the RBD that could be harnessed for vaccine development.

Identifiers

PMID32577644
PMCPMC7302197

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.