{
  "id": 6275429,
  "title": "Interferon redundancy counteracts proteolytic inactivation by SARS-CoV-2 3CL main protease",
  "url": "https://urgent.news/2026/09/08/interferon-redundancy-counteracts-proteolytic-inactivation-by-sars",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-08T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.07.749787v1?rss=1"
  },
  "original_language": "en",
  "account": "Interferons (IFNs) are protein molecules released by cells in response to a viral infection, which trigger antiviral defenses through phosphorylation of signal transducer and activator of transcription (STAT) proteins. Previous research discovered that the SARS-CoV-2 main protease, 3CLpro, was expelled from infected cells via gasdermin D/E pores and retained proteolytic activity in human serum against extracellular substrates. In this study, the researchers found that 3CLpro selectively cleaves and inactivates glycosylated interferons L1, L2, and a rare variant of interferon gamma (Arg160Gln), but does not affect wild-type interferon gamma, L3, L4, alpha or beta. The study identified the importance of O-linked glycosylation at specific sites of IFN-L1 and N-linked glycosylation at Asn65 for signaling. Surprisingly, the researchers observed that O-glycosylation was essential for the cleavage and inactivation of IFN-L1 by 3CLpro at two sites, leading to reduced STAT1 phosphorylation and impaired induction of IFN-stimulated proteins MX1, OAS2, and IFIT1. However, cleavage of IFN-L2 did not disrupt signaling or antiviral activity against SARS-CoV-2 and vesicular stomatitis virus. Additionally, the study revealed that matrix metalloproteinases (MMPs) 2, 7, 8, and 12 degrade 3CLpro, while 3CLpro does not affect these MMPs.",
  "summary": "Interferons (IFNs) are secreted during virus infection and induce antiviral responses through receptor-mediated phosphorylation of signal transducer and activator of transcription (STAT) proteins, leading to IFN-stimulated gene expression with antiviral activity. We previously reported that the SARS-CoV-2 main protease, 3CLpro, is secreted from infected cells through gasdermin D/E pores and…",
  "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."
}