Heptad repeat 1-derived N peptide inhibitors improve broad-spectrum anti-HIV-1 activity
Bibliographic record
Abstract
• N36 was modified by introducing FPPR or trimer motif MTQ, named FPPR-N36,MTQ-N36 and MTQ-FPPR-N36. • The three newly designed N-peptide inhibitors(NPIs) had inhibitory activity against HIV-1 infection, and IC50 of trimeric NPIs reached the nanomolar level. • FPPR-N36 might be a promising candidate NPI for suppressing HIV-1 strains that were resistant to conventional NPIs. HIV-1 N-peptide inhibitor (NPI) derived from N-terminal heptad-repeat region (HR1) of gp41 can target C-terminal heptad-repeat region (HR2) or the HR1 to interfere with the formation of endogenous six-helix bundle (6HB). However, the NPI is less active than the C-peptide inhibitor. In this study, we reported three HR1-derived NPIs designed by adding fusion peptide proximal region (FPPR) of gp41 or a trimeric motif MTQ into the N36 peptide and then evaluated their anti-HIV-1 activities. Molecular modeling was performed using Swiss Model. The inhibitory activity of NPIs on HIV-1 was assessed by Env-pseudovirus infection assays and cell-cell fusion assays. Interaction between NPIs and HR2 peptides was evaluated by circular dichroism and Native PAGE. The three newly designed NPIs, FPPR-N36, MTQ-N36, and MTQ-FPPR-N36, exhibited higher anti-HIV-1 activity than N36. The stability of the coiled-coil core formed by three designed NPIs or the 6HB formed by C34 and these NPIs were significantly higher than those of corresponding monomer N36 or isoleucine zipper-engineered trimeric N36 (IZN36). The 50 % inhibitory concentrations (IC 50 ) of MTQ-N36 against HIV-1 infection were at a nanomolar level, lower than those of other tested NPIs. The FPPR-N36 could also inhibit infection of HIV-1 strains that were resistant to N36 and IZN36. The three newly designed NPIs had inhibitory activity against HIV-1 infection. Among them, MTQ-N36 exhibited a higher potential to inhibit HIV-1 entry than other peptides, and FPPR-N36 might be a promising candidate NPI for suppressing HIV-1 strains that are resistant to conventional NPIs.
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".