Inhibitors of 3C Cysteine Proteinases from Picornaviridae
Bibliographic record
Abstract
The Picornaviridae are among the smallest icosahedral positive-sense single stranded RNA containing viruses known, and comprise one of the largest and most important families of human and animal pathogens. The hepatitis A virus (HAV) and human rhinovirus (HRV) are important pathogens that belong to the picornavirus family. All picornaviruses have a 3C proteinase that processes an initially biosynthesized precursor protein and is crucial for viral maturation and replication. Although it is a cysteine proteinase, this 3C enzyme has a topology similar to those of the chymotrypsin-like serine proteinases. A series of inhibitors of HAV and HRV 3C proteinases were synthesized and tested as potential lead compounds for the design of therapeutic agents for human picornaviral pathogens. This research shows that thiol-reactive groups or "warheads" such as iodoacetamides, beta-lactones, Michael acceptors, ketones and pseudoxazolones can be used as effective tools to inhibit the HAV and HRV 3C proteinase enzymes. In addition, studies based on enzyme-inhibitor kinetics, mass spectrometry and NMR spectroscopy were effectively used to gain knowledge concerning enzyme-inhibitor mechanism of action and enzyme-inhibitor regiospecific reactivity.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".