{
  "id": 17311114,
  "title": "A broadly active flavivirus NS4B targeting compound that blocks NS4B-NS3 binding and replication organelle formation",
  "url": "https://urgent.news/2026/10/30/a-broadly-active-flavivirus-ns4b-targeting-compound-that-blocks-ns4b",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-30T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.29.762806v1?rss=1"
  },
  "original_language": "en",
  "account": "A novel flavivirus NS4B-targeting compound, SRI-38841, has been discovered that effectively inhibits replication and blocks organelle formation in mosquito-borne viruses such as West Nile virus, dengue virus, Zika virus, and Japanese encephalitis virus. This xanthine analog, derived from earlier inhibitors, displays low cytotoxicity and high potency against the target viruses. When exposed to the viruses under compound selection, resistant strains developed mutations in the NS4B protein, which were subsequently analyzed using reverse genetics. These mutations were found to be located in regions similar to those involved in resistance to other NS4B inhibitors, such as JNJ-A07 and NITD-688. Docking studies revealed that SRI-38841 binds to a cytosolic-facing pocket on the NS4B protein, which differs from the model that places these residues in the ER lumen. Mutations in the predicted binding pocket (A45 and K56) resulted in resistance, while changes at other residues did not. Overall, these findings support the idea that SRI-38841 engages a unique cytosolic-facing pocket, making it a promising starting point for the development of effective, broad-spectrum orthoflavivirus antivirals.",
  "summary": "Mosquito-borne orthoflaviviruses, including West Nile virus (WNV), dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV), cause substantial global morbidity and mortality, yet no broadly effective direct-acting antivirals are available. The viral nonstructural protein NS4B has emerged as a promising antiviral target, although the compounds described to date are largely…",
  "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."
}