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Record W4292488032 · doi:10.1038/s41467-022-32262-8

SARS-CoV-2 variants of concern: spike protein mutational analysis and epitope for broad neutralization

2022· article· en· W4292488032 on OpenAlexafffund
Dhiraj Mannar, James W. Saville, Zehua Sun, Xing Zhu, Michelle M. Martí, Shanti Swaroop Srivastava, Alison Berezuk, Steven Zhou, Katharine S. Tuttle, Michele D. Sobolewski, Andrew Kim, Benjamin R. Treat, Priscila M. S. Castanha, Jana L. Jacobs, Simon M. Barratt‐Boyes, John W. Mellors, Dimiter S. Dimitrov, Wei Li, Sriram Subramaniam

Bibliographic record

VenueNature Communications · 2022
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsUniversity of British Columbia
FundersCanadian Institutes of Health ResearchMedical Center, University of PittsburghNational Institutes of HealthVictoria General Hospital FoundationCanada Excellence Research Chairs, Government of CanadaBritish Columbia Centre for Disease ControlGenome British ColumbiaUniversity of Pittsburgh
KeywordsNeutralizationSpike (software development)EpitopeGlycoproteinSpike ProteinBiologyMutationGeneticsAntibodySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)VirologyComputational biologyCoronavirus disease 2019 (COVID-19)GeneMedicine

Abstract

fetched live from OpenAlex

Abstract Mutations in the spike glycoproteins of SARS-CoV-2 variants of concern have independently been shown to enhance aspects of spike protein fitness. Here, we describe an antibody fragment (V H ab6) that neutralizes all major variants including the recently emerged BA.1 and BA.2 Omicron subvariants, with a unique mode of binding revealed by cryo-EM studies. Further, we provide a comparative analysis of the mutational effects within previously emerged variant spikes and identify the structural role of mutations within the NTD and RBD in evading antibody neutralization. Our analysis shows that the highly mutated Gamma N-terminal domain exhibits considerable structural rearrangements, partially explaining its decreased neutralization by convalescent sera. Our results provide mechanistic insights into the structural, functional, and antigenic consequences of SARS-CoV-2 spike mutations and highlight a spike protein vulnerability that may be exploited to achieve broad protection against circulating variants.

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 score0.001
Threshold uncertainty score0.002

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)0.0010.000

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 head0.068
GPT teacher head0.408
Teacher spread0.340 · 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

Citations68
Published2022
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicSARS-CoV-2 and COVID-19 ResearchFrench-language works237,207