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Record W2981372844 · doi:10.1128/jvi.01325-19

A New Family of Small-Molecule CD4-Mimetic Compounds Contacts Highly Conserved Aspartic Acid 368 of HIV-1 gp120 and Mediates Antibody-Dependent Cellular Cytotoxicity

2019· article· en· W2981372844 on OpenAlexafffund
Shilei Ding, Melissa C. Grenier‐Davies, William D. Tolbert, Dani Vézina, Rebekah Sherburn, Jonathan Richard, Jérémie Prévost, Jean-Philippe Chapleau, Gabrielle Gendron‐Lepage, Halima Medjahed, Cameron F. Abrams, Joseph Sodroski, Marzena Pazgier, Amos B. Smith, Andrés Finzi

Bibliographic record

VenueJournal of Virology · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicHIV Research and Treatment
Canadian institutionsUniversité de MontréalMcGill UniversityCentre Hospitalier de l’Université de Montréal
FundersSLAC National Accelerator LaboratoryBiological and Environmental ResearchBasic Energy SciencesNational Institute of Allergy and Infectious DiseasesFonds de Recherche du Québec - SantéCanadian Institutes of Health ResearchUniformed Services University of the Health SciencesNational Institute of General Medical SciencesamfAR, The Foundation for AIDS ResearchBrookhaven National LaboratoryU.S. Department of DefenseU.S. Department of EnergyOffice of ScienceCanada Research ChairsNational Institutes of HealthGovernment of Canada
KeywordsEpitopeAntibody-dependent cell-mediated cytotoxicityGlycoproteinAntibodyBiologySmall moleculeViral envelopeVirologyTrimerVirusProtein structureHuman immunodeficiency virus (HIV)Cell biologyCytotoxicityBiochemistryIn vitroChemistryGenetics

Abstract

fetched live from OpenAlex

HIV-1 has evolved multiple strategies to avoid humoral responses. One efficient mechanism is to keep its envelope glycoprotein (Env) in its "closed" conformation. Here, we report on a new family of small molecules that are able to "open up" Env, thus exposing vulnerable epitopes. This new family of molecules binds in the Phe43 cavity and contacts the highly conserved D368 residue. The structural and biological attributes of molecules of this family make them good candidates for drug development.

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 integrity0.0000.001
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 head0.014
GPT teacher head0.247
Teacher spread0.233 · 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

Citations40
Published2019
Admission routes2
Has abstractyes

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