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Record W4313315566 · doi:10.1038/s41467-022-35641-3

Force-tuned avidity of spike variant-ACE2 interactions viewed on the single-molecule level

2022· article· en· W4313315566 on OpenAlexafffund
Rong Zhu, Daniel Canena, Mateusz Sikora, Miriam Klausberger, Hannah Seferovic, Ahmad Reza Mehdipour, Lisa Hain, Elisabeth Laurent, Vanessa Monteil, Gerald Wirnsberger, Ralph Wieneke, Robert Tampé, Nikolaus F. Kienzl, Lukas Mach, Alì Mirazimi, Yoo Jin Oh, Josef Penninger, Gerhard Hummer, Peter Hinterdorfer

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsUniversity of British Columbia
FundersLeibniz-GemeinschaftCanadian Institutes of Health ResearchInnovative Medicines InitiativeVolkswagen FoundationAustrian Science FundLeibniz-RechenzentrumÖsterreichischen Akademie der WissenschaftenUniversität für Bodenkultur WienEuropean Federation of Pharmaceutical Industries and AssociationsVienna Science and Technology FundEuropean CommissionHorizon 2020 Framework ProgrammeMax-Planck-GesellschaftDeutsche Forschungsgemeinschaft
KeywordsAvidityInfectivityChemistryMoleculeBiophysicsSpike (software development)Spike ProteinReceptorViral entryBiologyCoronavirus disease 2019 (COVID-19)VirusViral replicationVirologyGeneticsBiochemistryAntibodyMedicine

Abstract

fetched live from OpenAlex

Recent waves of COVID-19 correlate with the emergence of the Delta and the Omicron variant. We report that the Spike trimer acts as a highly dynamic molecular caliper, thereby forming up to three tight bonds through its RBDs with ACE2 expressed on the cell surface. The Spike of both Delta and Omicron (B.1.1.529) Variant enhance and markedly prolong viral attachment to the host cell receptor ACE2, as opposed to the early Wuhan-1 isolate. Delta Spike shows rapid binding of all three Spike RBDs to three different ACE2 molecules with considerably increased bond lifetime when compared to the reference strain, thereby significantly amplifying avidity. Intriguingly, Omicron (B.1.1.529) Spike displays less multivalent bindings to ACE2 molecules, yet with a ten time longer bond lifetime than Delta. Delta and Omicron (B.1.1.529) Spike variants enhance and prolong viral attachment to the host, which likely not only increases the rate of viral uptake, but also enhances the resistance of the variants against host-cell detachment by shear forces such as airflow, mucus or blood flow. We uncover distinct binding mechanisms and strategies at single-molecule resolution, employed by circulating SARS-CoV-2 variants to enhance infectivity and viral transmission.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.145
GPT teacher head0.408
Teacher spread0.263 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations45
Published2022
Admission routes2
Has abstractyes

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