ArticleJournal of virology2023
SARS-CoV-2 Omicron entry is type II transmembrane serine protease-mediated in human airway and intestinal organoid models.
Article in Journal of virology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 47 citations in OpenAlex.
- Recent Advances in the Design of Inhibitors Targeting the Viral Entry and Replication of the SARS-CoV-2 Virus, Driven by In Silico Approaches.Molecules (Basel, Switzerland) · 2026Review
- Intestinal Organoids as Models to Study Viruses: Current Application and Future Perspective.Journal of microbiology and biotechnology · 2026Review
- Repurposing screens reveal a role for PKCη and NF1 in SARS-CoV-2 infection.PLoS pathogens · 2026Article
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- Organoids: From Bench to Bedside Applications.MedComm · 2026Review
- TMPRSS2-mediated coronavirus spike activation and inhibition.Nature structural & molecular biology · 2026Article
- Integrated Evaluation ofPharmaceuticals (Basel, Switzerland) · 2026Article
- Organoids Gone Viral: A Comprehensive Review on Human Organoid Models to Study Viral Pathogenesis.Viruses · 2026Review
- Central role of glycosylation processes in human genetic susceptibility to SARS-CoV-2 infections with Omicron variants.Nature genetics · 2026Article
- Stealth replication of SARS-CoV-2 Omicron in the nasal epithelium at physiological temperature.Journal of virology · 2026Article
- Searching for Novel Antiviral Agents as COVID19 Treatments: Guanidino Diaryl Thioureas.ChemMedChem · 2026Article
- Identification of Cathepsin L as the Molecular Target of Hydroxychloroquine With Chemical Proteomics.Molecular & cellular proteomics : MCP · 2025Article
- Old World alphaviruses use distinct mechanisms to infect brain microvascular endothelial cells for neuroinvasion.Cell reports · 2025Article
- Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases.iScience · 2025Article
- Organoid-based neutralization assays reveal a distinctive profile of SARS-CoV-2 antibodies and recapitulate the real-world efficacy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Simulations and active learning enable efficient identification of an experimentally-validated broad coronavirus inhibitor.Nature communications · 2025Article
- An orally available MNature communications · 2025Article
- Host susceptibilities and entry processes of SARS-CoV-2 Omicron variants using pseudotyped viruses carrying spike protein.BMC veterinary research · 2025Article
- CRISPR-Cas9 genetic screens reveal regulation of TMPRSS2 by the Elongin BC-VHL complex.Scientific reports · 2025Article
- The respective roles of TMPRSS2 and cathepsins for SARS-CoV-2 infection in human respiratory organoids.Journal of virology · 2025Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2 can enter cells after its spike protein is cleaved by either type II transmembrane serine proteases (TTSPs), like TMPRSS2, or cathepsins. It is now widely accepted that the Omicron variant uses TMPRSS2 less efficiently and instead enters cells via cathepsins, but these findings have yet to be verified in more relevant cell models. Although we could confirm efficient cathepsin-mediated entry for Omicron in a monkey kidney cell line, experiments with protease inhibitors showed that Omicron (BA.1 and XBB1.5) did not use cathepsins for entry into human airway organoids and instead utilized TTSPs. Likewise, CRISPR-edited intestinal organoids showed that entry of Omicron BA.1 relied on the expression of the serine protease TMPRSS2 but not cathepsin L or B. Together, these data force us to rethink the concept that Omicron has adapted to cathepsin-mediated entry and indicate that TTSP inhibitors should not be dismissed as prophylactic or therapeutic antiviral strategy against SARS-CoV-2. IMPORTANCE Coronavirus entry relies on host proteases that activate the viral fusion protein, spike. These proteases determine the viral entry route, tropism, host range, and can be attractive drug targets. Whereas earlier studies using cell lines suggested that the Omicron variant of SARS-CoV-2 has changed its protease usage, from cell surface type II transmembrane serine proteases (TTSPs) to endosomal cathepsins, we report that this is not the case in human airway and intestinal organoid models, suggesting that host TTSP inhibition is still a viable prophylactic or therapeutic antiviral strategy against current SARS-CoV-2 variants and highlighting the importance of relevant human
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