Soraphen A: A Probe for Investigating the Role of de Novo Lipogenesis during Viral Infection
Bibliographic record
Abstract
Many viruses including the hepatitis C virus (HCV) induce changes to the infected host cell metabolism that include the up-regulation of lipogenesis to create a favorable environment for the virus to propagate. The enzyme acetyl-CoA carboxylase (ACC) polymerizes to form a supramolecular complex that catalyzes the rate-limiting step of de novo lipogenesis. The small molecule natural product Soraphen A (SorA) acts as a nanomolar inhibitor of acetyl-CoA carboxylase activity through disruption of the formation of long highly active ACC polymers from less active ACC dimers. We have shown that SorA inhibits HCV replication in HCV cell culture models expressing subgenomic and full-length replicons (IC50 = 5 nM) as well as a cell culture adapted virus. Using coherent anti-Stokes Raman scattering (CARS) microscopy, we have shown that SorA lowers the total cellular lipid volume in hepatoma cells, consistent with a reduction in de novo lipogenesis. Furthermore, SorA treatment was found to depolymerize the ACC complexes into less active dimers. Taken together, our results suggest that SorA treatment reverses HCV-induced lipid accumulation and demonstrate that SorA is a valuable probe to study the roles of ACC polymerization and enzymatic activity in viral pathogenesis.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".