{
  "abstract": "Pre-existing state of the host cell is a major determinant of the host susceptibility to viral infection. Here, we identify the epithelial-mesenchymal transition transcription factor Snail as a host restriction factor for SARS-CoV-2. Snail loss markedly increased SARS-CoV-2 replication, whereas Snail overexpression and complementation restricted viral replication. Transcriptomic analysis of Snail knockout cells revealed remodelling of epithelial surface-associated programs, including apical membrane, brush border, and junctional pathways. ACE2, the cellular receptor for SARS-CoV-2, was among the genes upregulated in Snail knockout cells. Snail negatively regulated ACE2 transcription, leading to reduced ACE2 transcript and protein abundance and, consequently, lower SARS-CoV-2 entry. Consistent with this, ACE2 promoter activity was higher in Snail knockout cells, which was reduced following Snail complementation. As a means to counter Snail's antiviral functions, SARS-CoV-2 infection progressively depleted Snail protein in different cell culture models, while SNAI1 transcript abundance was surprisingly maintained or increased under the same conditions. Proteasome inhibition and protein-turnover analyses failed to account for this depletion. We find that SARS-CoV-2 infection resulted in reduced association of SNAI1 with polysomes at later stages of infection coinciding with virus-induced host translational suppression, resulting in lower protein synthesis. Together, these findings identify Snail as a regulator of the epithelial entry landscape that limits ACE2-associated SARS-CoV-2 entry and shapes cellular permissiveness, with broader implications for cellular determinants of viral tropism. SARS-CoV-2, in turn, progressively depletes this short-lived antiviral regulator, revealing how virus-induced translational shutoff can remodel pre-existing host cell states and thereby alter cellular susceptibility during infection.",
  "abstract_shown": true,
  "affiliations": [
    "Academy of Scientific and Innovative Research"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "P. P. Sahoo"
    },
    {
      "name": "V. Sah"
    },
    {
      "affs": [
        0
      ],
      "name": "K. Harinivas Harshan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f95108qh59jx2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.20.760609",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760609v1.full",
  "id": "f95108qh59jx2",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760609v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7223088015",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760609v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f95108qh59jx2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:58Z",
      "native_id": "10.64898/2026.10.20.760609",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.20.760609v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Snail restricts SARS-CoV-2 entry by limiting ACE2 expression as part of broader remodelling of epithelial determinants of viral tropism",
  "title_text": "Snail restricts SARS-CoV-2 entry by limiting ACE2 expression as part of broader remodelling of epithelial determinants of viral tropism",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:58Z",
  "url": "https://research.draconitic.com/paper/f95108qh59jx2",
  "venue": "bioRxiv",
  "versions": []
}