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Record W2138921145 · doi:10.1002/9780470048672.wecb109

Viral Cysteine Peptidases and Cysteine Peptidase Inhibitors

2008· other· en· W2138921145 on OpenAlexaff
Michael N.G. James

Bibliographic record

VenueWiley Encyclopedia of Chemical Biology · 2008
Typeother
Languageen
FieldMedicine
TopicPeptidase Inhibition and Analysis
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsCysteineSerineNS2-3 proteaseBiologyRNABiochemistryEnzymeCatalytic triadVirusVirologyViral replicationGene

Abstract

fetched live from OpenAlex

Abstract Polyprotein processing is a controlled cascade of proteolytic events carried out by virally encoded cysteine proteinases. It plays a central role in the infectious life cycle of animal RNA viruses such as picornaviruses, caliciviruses, and coronaviruses. Furthermore, some of these viral enzymes are vitally important in viral RNA genome replication, virion assembly, and virus–host antagonism. The 3 C pro and 3 C‐like (3CL pro ) peptidases are structurally related to the chymotrypsin branch of the serine proteinase family, but they have the catalytic serine residue replaced by a cysteine. Their uniquely designed yet structurally conserved S1 substrate binding pocket strongly favors a P1‐Glutamine in the substrate. The high level of structural conservation in the active sites of 3 C pro and 3CL pro and the lack of a mammalian homolog make these enzymes hotly pursued targets for antiviral drug design. The structures of these viral cysteine peptidases in complex with various inhibitors have shed light not only on how different inhibitors work but also on the catalytic mechanisms underlying the hydrolysis of normal peptidyl substrates. Most importantly, the results from the structural studies on Hepatitis A virus (HAV) 3 C pro point out possible new directions in the design of therapeutic intervention in a variety of diseases caused by members of these large RNA virus families.

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: Not applicable · Consensus signal: none
GenreCandidate signal: Other · Consensus signal: none
Teacher disagreement score0.004
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0040.001

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 head0.007
GPT teacher head0.246
Teacher spread0.239 · 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 designNot applicable
Domainnot available
GenreOther

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
Published2008
Admission routes1
Has abstractyes

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