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Repurposing of Relatively Large Drugs for the Receptor Binding Domain of SARS-CoV-2 Spike Protein

2022· preprint· en· W4220976012 on OpenAlexaff
Mansour H. Almatarneh, A.A. Al-Qaisia, Amani Al-Shantia, Abd Al‐Aziz A. Abu‐Saleh

Bibliographic record

Venuenot available
Typepreprint
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsMemorial University of Newfoundland
Fundersnot available
KeywordsDrug repositioningRepurposingSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Computational biologyDocking (animal)Coronavirus disease 2019 (COVID-19)Drug discoveryDrug developmentSpike ProteinDrug2019-20 coronavirus outbreakPharmacologyAtazanavirChemistryBiologyVirologyMedicineInfectious disease (medical specialty)BiochemistryHuman immunodeficiency virus (HIV)DiseaseViral load

Abstract

fetched live from OpenAlex

Nowadays, there are a few therapeutics to prevent or treat COVID-19. Because the development of safe and effective drugs is expensive and time-consuming, drug repurposing is now part of the arsenal of drug discovery. Herein, we focus on the repurposing of relatively large FDA-approved drugs (MW > 500, LogP ≤ 5) that target the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. We performed a computational study incorporating molecular docking, molecular dynamics simulations, and relative binding energy calculations to discover prospective compounds with high affinity towards the viral RBD. We found that the most promising drugs, namely, Atazanavir, Zazole, Valrubicin, and Telotristat, influence hotspot residues of the RBD protein and may interfere with the human angiotensin-converting enzyme-2 (ACE2) receptor. Our findings corroborate with the present literature and can accelerate the rational design of selective inhibitors against SARS-CoV-2.

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)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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 head0.064
GPT teacher head0.359
Teacher spread0.295 · 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 designSimulation or modeling
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

Citations1
Published2022
Admission routes1
Has abstractyes

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