{
  "id": 7683894,
  "title": "A rational design strategy and validation for protease-resistant fusion-inhibitor antiviral peptides",
  "url": "https://urgent.news/2026/09/15/a-rational-design-strategy-and-validation-for-protease-resistant",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-15T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.12.750390v1?rss=1"
  },
  "original_language": "en",
  "account": "Peptide-based fusion inhibitors show promise in combating enveloped viruses that require membrane fusion for infecting host cells. However, these peptide therapies have faced challenges due to their instability within the body. In this study, researchers identified a key protease called Transmembrane Protease, Serine 2 (TMPRSS2) that efficiently degrades peptide inhibitors with the wildtype sequence of the heptad repeat 2 (HR2) domain from the SARS-CoV-2 spike protein. This protease plays a crucial role in the SARS-CoV-2 virus-cell fusion process. Utilizing deep mutational scanning and natural occurrence, the team designed three protease-resistant peptides and evaluated their inhibitory activity in a cell-cell fusion assay. All three candidates demonstrated inhibitory effects. A high-resolution cryo-EM structure of the top candidate, HR2-NHN, bound to its HR1 target revealed the molecular basis for its enhanced effectiveness. When tested in both a virus-cell infection assay and a mouse model, the top candidate showed significantly improved efficacy compared to the wildtype peptide when administered 12 hours prior to infection. These findings suggest that the design strategies employed for creating protease-resistant peptides could be adapted to target other enveloped viruses, offering a potential avenue for the development of safe and prophylactic antiviral therapies that can be administered before exposure.",
  "summary": "Peptide-based fusion inhibitors are promising pharmaceuticals in the fight against enveloped viruses relying on membrane fusion for host infection. However, peptide therapeutic applications have long been hindered by their poor stability in vivo. Here, we discovered that peptide inhibitors with the wildtype sequence of the heptad repeat 2 (HR2) domain of the SARS-CoV-2 spike protein are…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}