Evidence map›Paper›PMID 32678978›Full record

ArticleAnalytical chemistry2020

The Utility of Native MS for Understanding the Mechanism of Action of Repurposed Therapeutics in COVID-19: Heparin as a Disruptor of the SARS-CoV-2 Interaction with Its Host Cell Receptor.

Yang Yang, Yi Du, Igor A Kaltashov

Open access · bronzeAbstract read
In one paragraph

Article in Analytical chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.8field-weighted citation impact, top 3% of its field
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

32 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Article
  3. The accomplices: Heparan sulfates and N-glycans foster SARS-CoV-2 spike:ACE2 receptor binding and virus priming.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  4. Review
  5. Article
  6. Article
  7. Uncovering the Role ofJournal of the American Chemical Society · 2023
    Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Glycosylation is a key in SARS-CoV-2 infection.Journal of molecular medicine (Berlin, Germany) · 2021
    Review
  20. Polysulfates Block SARS-CoV-2 Uptake through Electrostatic Interactions*.Angewandte Chemie (International ed. in English) · 2021
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Yang YangDepartment of Chemistry, University of Massachusetts-Amherst, 240 Thatcher Way, Amherst, Massachusetts 01003, United States.
Yi DuDepartment of Chemistry, University of Massachusetts-Amherst, 240 Thatcher Way, Amherst, Massachusetts 01003, United States.
Igor A KaltashovDepartment of Chemistry, University of Massachusetts-Amherst, 240 Thatcher Way, Amherst, Massachusetts 01003, United States.ORCID 0000-0002-4355-6039
University of Massachusetts Amherst · US

Funding

An integrated mass spectrometry approach to study heparin structure-bioactivityR01GM112666 · NIGMS · UNIVERSITY OF MASSACHUSETTS AMHERST · PI KALTASHOV, IGOR A · 2016 to 2024
$3.0M
NIGMS NIH HHS R01 GM112666
6 · The paper itself

Abstract

The emergence and rapid proliferation of the novel coronavirus (SARS-CoV-2) resulted in a global pandemic, with over 6,000,000 cases and nearly 400,000 deaths reported worldwide by the end of May 2020. A rush to find a cure prompted re-evaluation of a range of existing therapeutics vis-à-vis their potential role in treating COVID-19, placing a premium on analytical tools capable of supporting such efforts. Native mass spectrometry (MS) has long been a tool of choice in supporting the mechanistic studies of drug/therapeutic target interactions, but its applications remain limited in the cases that involve systems with a high level of structural heterogeneity. Both SARS-CoV-2 spike protein (S-protein), a critical element of the viral entry to the host cell, and ACE2, its docking site on the host cell surface, are extensively glycosylated, making them challenging targets for native MS. However, supplementing native MS with a gas-phase ion manipulation technique (limited charge reduction) allows meaningful information to be obtained on the noncovalent complexes formed by ACE2 and the receptor-binding domain (RBD) of the S-protein. Using this technique in combination with molecular modeling also allows the role of heparin in destabilizing the ACE2/RBD association to be studied, providing critical information for understanding the molecular mechanism of its interference with the virus docking to the host cell receptor. Both short (pentasaccharide) and relatively long (eicosasaccharide) heparin oligomers form 1:1 complexes with RBD, indicating the presence of a single binding site. This association alters the protein conformation (to maximize the contiguous patch of the positive charge on the RBD surface), resulting in a notable decrease in its ability to associate with ACE2. The destabilizing effect of heparin is more pronounced in the case of the longer chains due to the electrostatic repulsion between the low-p

Indexed as

Angiotensin-Converting Enzyme 2BetacoronavirusBinding SitesCoronavirus InfectionsCOVID-19GasesHeparinHumansMass SpectrometryMolecular Dynamics SimulationPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein BindingProtein DomainsRecombinant ProteinsACE2 protein, humanAngiotensin-Converting Enzyme 2GasesHeparinPeptidyl-Dipeptidase ARecombinant ProteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID32678978
PMCPMC7384394
OpenAlexW3043005553

What OpenQuestion holds

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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 OpenQuestion graph.