FGFR signaling and neddylation facilitate SARS-CoV-2 infection by modulating interferon induction and viral entry, respectively
Bibliographic record
Abstract
SARS-CoV-2 is the causative agent of COVID-19, and although vaccines have reduced disease severity, emerging variants remain a significant public health issue. Broadly effective therapeutics, particularly those targeting host pathways essential for coronavirus infection, are still needed. Here, we used a CRISPR knockout screen to identify druggable host factors required for SARS-CoV-2 infection. The screen revealed NAE1 and FGFR1 as key contributors to infection. Inhibitors, either FDA-approved or those in clinical trials, of these pathways reduced replication of both ancestral and contemporary viral variants. Mechanistic studies showed that FGFR1 promotes viral replication through downstream MEK/ERK signaling, while neddylation appears to support viral entry or infectivity rather than replication itself. In a murine model of severe COVID-19, inhibitors of NAE1 and FGFR1 significantly decreased viral load and lung pathology. These findings support the development of host-targeted antiviral strategies.
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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 | 0.007 |
| 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 | 0.000 |
| 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".