Evidence map›Paper›PMID 40461447›Full record

ArticleNature communications2025

Unveiling the structural spectrum of SARS-CoV-2 fusion by in situ cryo-ET.

Caner Akıl, Jialu Xu, Juan Shen, Peijun Zhang

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Switching Spike Plasticity Shapes ACE2 Engagement Across SARS-CoV-2 Variants.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Frontiers in cell and developmental biology · 2026
    Review
  15. Review
  16. Article
  17. Review
  18. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Caner Akıl *Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK.ORCID http://orcid.org/0000-0002-9464-1903
Jialu Xu *Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Juan ShenDivision of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Peijun ZhangChinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, UK. peijun.zhang@strubi.ox.ac.uk.ORCID http://orcid.org/0000-0003-1803-691X

Funding

Project 3. IntegrationU54AI170791 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Zandrea Ambrose · 2022 to 2026
$30.6M
Technology Development 2: MAS NMR and dynamic nuclear polarization for HIV-1 structural biologyP50AI150481 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI XIONG, YONG · 2019 to 2021
$14.1M
Correlative cryoET of the HIV-1 integration targeting in native T-lymphocytesR21AI184080 · NIAID · UNIVERSITY OF OXFORD · PI ZHANG, PEIJUN · 2024 to 2025
$285k
EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 101021133European Research Council 101021133NIAID NIH HHS P50 AI150481NIAID NIH HHS R21 AI184080NIAID NIH HHS U54 AI170791U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) P50AI150481U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R21AI184080Wellcome Trust 206422Wellcome Trust 311427Wellcome Trust (Wellcome) 206422/Z/17/ZWellcome Trust (Wellcome) 311427/Z/24/Z
6 · The paper itself

Abstract

SARS-CoV-2 entry into host cells is mediated by the spike protein, which drives membrane fusion. While cryo-EM reveals stable prefusion and postfusion conformations of the spike, the transient fusion intermediate states during the fusion process remain poorly understood. Here, we design a near-native viral fusion system that recapitulates SARS-CoV-2 entry and use cryo-electron tomography (cryo-ET) to capture fusion intermediates leading to complete fusion. The spike protein undergoes extensive structural rearrangements, progressing through extended, partially folded, and fully folded intermediates prior to fusion-pore formation, a process that depends on protease cleavage and is inhibited by the WS6 S2 antibody. Upon interaction with ACE2 receptor dimer, spikes cluster at membrane interfaces and following S2' cleavage concurrently transition to postfusion conformations encircling the hemifusion and initial fusion pores in a distinct conical arrangement. S2' cleavage is indispensable for advancing fusion intermediates to the fully folded postfusion state, culminating in membrane integration. Subtomogram averaging reveals that the WS6 S2 antibody binds to the spike's stem-helix, crosslinks and clusters prefusion spikes, as well as inhibits refolding of fusion intermediates. These findings elucidate the entire process of spike-mediated fusion and SARS-CoV-2 entry, highlighting the neutralizing mechanism of S2-targeting antibodies.

Indexed as

SARS-CoV-2Spike Glycoprotein, CoronavirusVirus InternalizationAngiotensin-Converting Enzyme 2AnimalsCOVID-19Cryoelectron MicroscopyElectron Microscope TomographyHumansMembrane FusionProtein ConformationACE2 protein, humanAngiotensin-Converting Enzyme 2Spike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID40461447
PMCPMC12134289

What OpenQuestion holds

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LicenceCC BY
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 OpenQuestion graph.