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Record W4225822226 · doi:10.1016/j.celrep.2021.110210

Structural basis and mode of action for two broadly neutralizing antibodies against SARS-CoV-2 emerging variants of concern

2021· article· en· W4225822226 on OpenAlexaff
Wenwei Li, Yaozong Chen, Jérémie Prévost, Irfan Ullah, Maolin Lu, Shang Yu Gong, Alexandra Tauzin, Romain Gasser, Dani Vézina, Sai Priya Anand, Guillaume Goyette, Debashree Chaterjee, Shilei Ding, William D. Tolbert, Michael W. Grunst, Yuxia Bo, Shijian Zhang, Jonathan Richard, Fei Zhou, Rick Huang, Lothar Esser, Allison Zeher, Marceline Côté, Priti Kumar, Joseph Sodroski, Di Xia, Pradeep D. Uchil, Marzena Pazgier, Andrés Finzi, Walther Mothes

Bibliographic record

VenueCell Reports · 2021
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsUniversity of OttawaUniversité de MontréalMcGill UniversityCentre Hospitalier de l’Université de Montréal
FundersNational Institute of Allergy and Infectious Diseases
KeywordsImmunogenEpitopeBiologyVirologyAntibodyMonoclonal antibodyNeutralizing antibodyImmune systemCoronavirusCell biologyCoronavirus disease 2019 (COVID-19)ImmunologyMedicine

Abstract

fetched live from OpenAlex

Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here, we elucidate the structural basis and mode of action for two potent SARS-CoV-2 spike (S)-neutralizing monoclonal antibodies, CV3-1 and CV3-25, which remain effective against emerging variants of concern in vitro and in vivo. CV3-1 binds to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the "RBD-up" position and triggers potent shedding of the S1 subunit. In contrast, CV3-25 inhibits membrane fusion by binding to an epitope in the stem helix region of the S2 subunit that is highly conserved among β-coronaviruses. Thus, vaccine immunogen designs that incorporate the conserved regions in the RBD and stem helix region are candidates to elicit pan-coronavirus protective immune responses.

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 score0.004

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 head0.078
GPT teacher head0.394
Teacher spread0.316 · 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

Citations144
Published2021
Admission routes1
Has abstractyes

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Same venueCell ReportsSame topicSARS-CoV-2 and COVID-19 ResearchFrench-language works237,207