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Record W4387212452 · doi:10.1016/j.jiph.2023.09.020

Exploring the structural and molecular interaction landscape of nirmatrelvir and Mpro complex: The study might assist in designing more potent antivirals targeting SARS-CoV-2 and other viruses

2023· article· en· W4387212452 on OpenAlexaff
Chiranjib Chakraborty, Manojit Bhattacharya, Abdulrahman Alshammari, Metab Alharbi, Thamer H. Albekairi, Chunfu Zheng

Bibliographic record

VenueJournal of Infection and Public Health · 2023
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsUniversity of Calgary
FundersKing Saud University
KeywordsComputational biologySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)MacromoleculeProteomeMolecular dynamicsChemistryBiologyBioinformaticsMedicineInfectious disease (medical specialty)BiochemistryComputational chemistry

Abstract

fetched live from OpenAlex

Several therapeutics have been developed and approved against SARS-CoV-2 occasionally; Nirmatrelvir is one of them. The drug target of nirmatrelvir is Mpro, and therefore, it is necessary to comprehend the structural and molecular interaction of the Mpro-nirmatrelvir complex. Integrative bioinformatics, system biology, and statistical models were used to analyze the macromolecular complex. Using two macromolecular complexes, the study illustrated the interactive residues, H-bonds, and interactive interfaces. It informed of six and nine H-bond formations for the first and second complex, respectively. The maximum bond length was observed as 3.33 Å. The ligand binding pocket's surface area and volume were noted as 303.485 Å2 and 295.456 Å3 for the first complex and 308.397 Å2 and 304.865 Å3 for the second complex. The structural proteome dynamics were evaluated by analyzing the complex's NMA mobility, eigenvalues, deformability, and B-factor. Conversely, a model was created to assess the therapeutic status of nirmatrelvir. Our study reveals the structural and molecular interaction landscape of Mpro-nirmatrelvir complex. The study will guide researchers in designing more broad-spectrum antiviral molecules mimicking nirmatrelvir, which assist in fighting against SARS-CoV-2 and other infectious viruses. It will also help to prepare for future epidemics or pandemics.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.158
Threshold uncertainty score0.237

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.001
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.218
GPT teacher head0.405
Teacher spread0.187 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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

Citations24
Published2023
Admission routes1
Has abstractyes

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