Copper(II) Inhibition of the SARS‐CoV‐2 Main Protease
Bibliographic record
Abstract
ABSTRACT In an analysis of the structural stability of the coronavirus main protease (Mpro), we identified regions of the protein that could be disabled by cobalt(III)‐cation binding to histidines and cysteines. Here we have extended our work to include copper(II) chelates, which we have docked to HIS 41 and CYS 145 in the Mpro active‐site region. We have found stable docked structures where Cu(II) could readily bond to the CYS 145 thiolate, which would be lethal to the enzyme. We investigated the structural basis of Cu(II) Schiff‐base chelates as potential Mpro inhibitors in silico. Using induced‐fit docking (IFD) and molecular dynamics (MD) simulations, we identified the binding mode and assessed the stability of Mpro inhibition. Our results show that Cu(II) chelates form stable complexes with HIS 41 and CYS 145, with Cu(II) bonding to the CYS 145 thiolate. This irreversible binding is anticipated to effectively inhibit Mpro activity, thereby preventing the proteolytic processing of the SARS‐CoV‐2 polyprotein into functional proteins necessary for viral activity. Our findings suggest that Cu(II) Schiff‐base chelates are promising candidates for the irreversible inhibition of SARS‐CoV‐2 Mpro.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
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 teacher head, 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".