Evidence map›Paper›PMID 12885899›Full record

ArticleJournal of virology2003

The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex.

Berend Jan Bosch, Ruurd van der Zee, Cornelis A M de Haan, Peter J M Rottier

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05648110 (A Phase I/III Randomized, Double-blind Study to Evaluate the Safety, Efficacy and Neutralizing Activity of AZD5156/AZD3152 for Pre-exposure Prophylaxis of COVID-19 in Participants With Conditions Causing Immune Impairment. Sub-study), which is not on this map. Cited by 890 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
890citing papers in PubMed, 2 pooled it
23.3field-weighted citation impact, top 1% 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.

NCT05648110 phase2 / phase3completednot on this mapstarted 2022, after this paper: background citation

A Phase I/III Randomized, Double-blind Study to Evaluate the Safety, Efficacy and Neutralizing Activity of AZD5156/AZD3152 for Pre-exposure Prophylaxis of COVID-19 in Participants With Conditions Causing Immune Impairment. Sub-study: Phase II Open Label Sub-study to Evaluate the Safety, PK, and Neutralizing Activity of AZD3152 for Pre-exposure Prophylaxis of COVID-19

TypeinterventionalSponsorAstraZenecaRan2022 to 2025Enrolled3,882ConditionsCOVID-19, SARS-CoV-2ArmsAZD5156 (Parent study Sentinel Safety Cohort), Placebo (Parent study Sentinel Safety Cohort), EVUSHELD™ (Parent study Main Cohort), AZD3152 (Parent study Main Cohort), Placebo (Parent study Main Cohort)
3 · Its place in the literature

Who cites it

890 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,568 citations in OpenAlex.

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  10. Computational design of an ultrapotent deltacoronavirus miniprotein inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2026
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830 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Berend Jan BoschVirology Division, Department of Infectious Diseases and Immunity, Faculty of Veterinary Medicine, and Institute of Biomembranes, Utrecht University, 3584 CL Utrecht, The Netherlands.
Ruurd van der Zee
Cornelis A M de Haan
Peter J M Rottier
Utrecht University · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Coronavirus entry is mediated by the viral spike (S) glycoprotein. The 180-kDa oligomeric S protein of the murine coronavirus mouse hepatitis virus strain A59 is posttranslationally cleaved into an S1 receptor binding unit and an S2 membrane fusion unit. The latter is thought to contain an internal fusion peptide and has two 4,3 hydrophobic (heptad) repeat regions designated HR1 and HR2. HR2 is located close to the membrane anchor, and HR1 is some 170 amino acids (aa) upstream of it. Heptad repeat (HR) regions are found in fusion proteins of many different viruses and form an important characteristic of class I viral fusion proteins. We investigated the role of these regions in coronavirus membrane fusion. Peptides HR1 (96 aa) and HR2 (39 aa), corresponding to the HR1 and HR2 regions, were produced in Escherichia coli. When mixed together, the two peptides were found to assemble into an extremely stable oligomeric complex. Both on their own and within the complex, the peptides were highly alpha helical. Electron microscopic analysis of the complex revealed a rod-like structure approximately 14.5 nm in length. Limited proteolysis in combination with mass spectrometry indicated that HR1 and HR2 occur in the complex in an antiparallel fashion. In the native protein, such a conformation would bring the proposed fusion peptide, located in the N-terminal domain of HR1, and the transmembrane anchor into close proximity. Using biological assays, the HR2 peptide was shown to be a potent inhibitor of virus entry into the cell, as well as of cell-cell fusion. Both biochemical and functional data show that the coronavirus spike protein is a class I viral fusion protein.

Indexed as

Amino Acid SequenceBase SequenceCircular DichroismCoronavirusDNA PrimersMembrane FusionMembrane GlycoproteinsMicroscopy, ElectronMolecular Sequence DataSequence Homology, Amino AcidSpike Glycoprotein, CoronavirusViral Envelope ProteinsDNA PrimersMembrane GlycoproteinsSpike Glycoprotein, Coronavirusspike glycoprotein, SARS-CoVspike protein, mouse hepatitis virusViral Envelope Proteins

Identifiers

PMID12885899
PMCPMC167208
OpenAlexW2097188280

What OpenQuestion holds

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Registered trials

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.