TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes
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Abstract
The SARS-CoV-2 virus infects cultured ACE2-expressing human enterocytes aided by the TMPRSS2 and TMPRSS4 serine proteases.
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Over 2,000 CFTR mutations have been reported, but small molecule therapeutics deployed clinically target only a subset of them.
“Over 2,000 mutations have been reported, yet small molecule therapeutics deployed clinically only target a subset of these185,186.”
From Organoids (2022) · cites this paper as [186]
The Materials and Methods section describes intestinal enteroids used to study SARS-CoV-2, and the Results section discusses protease inhibition during infection; neither addresses CFTR mutations or clinical CFTR therapies. Searches for “CFTR mutations 2,000” and “small molecule therapeutics clinically target subset of CFTR mutations” found no relevant passage in our copy. (LLM, conf=0.77)
Experimental — accuracy not yet measuredCystic fibrosis is a genetic disorder caused by mutations in CFTR, which encodes a transmembrane chloride and bicarbonate transporter.
“Cystic fibrosis (CF) is a genetic disorder caused by mutations in the gene CFTR, which expresses a transmembrane chloride and bicarbonate transporter.”
From Organoids (2022) · cites this paper as [186]
The Introduction and Results discuss SARS-CoV-2 infection of intestinal cells and the roles of ACE2, TMPRSS2, and TMPRSS4; page numbers are not available in our copy. Searches for cystic fibrosis, CFTR, and a chloride and bicarbonate transporter found no passage addressing the claim. (LLM, conf=0.75)
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SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis
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- Authors
- Zang, R., Castro, M. F. G., McCune, B. T., Zeng, Q., Rothlauf, P. W., Sonnek, N. M., Liu, Z., Brulois, K. F., Wang, X., Greenberg, H. B., Diamond, M. S., Ciorba, M. A., Whelan, S. P. J., & Ding, S.
- Affiliations
- Washington University in St. Louis (US)
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
- Harvard University (US)
- Division of Gastroenterology, Department of Medicine, Washington School of Medicine, St. Louis, MO, USA.
- VA Palo Alto Health Care System (US)
- Ocean University of China (CN)
- Corresponding author
- Ding, Siyuan
- ORCID
- Venue
- Science Immunology
- Published
- 2020-05-19
- Volume
- 5
- Issue
- 47
- ISSN
- 2470-9468 (ISSN-L)
- PMC
- PMC7285829
- OpenAlex
- W3025559601
- Cited by
- 982
- References
- 73
- Citations by year
- 2026: 33 · 2025: 53 · 2024: 84 · 2023: 115 · 2022: 190 · 2021: 315 · 2020: 190 · 2012: 1
- FWCI
- 26.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Science Immunology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R00 AI135031, R01 AI150796, R01 AI125249, R01 AI127828, 75N93019C00062, R37 AI059371)
- U.S. Department of Veterans Affairs (GRH0022)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30 DK052574, R01 DK109384)
- Defense Advanced Research Projects Agency (HR001117S0019)
- National Institute of Allergy and Infectious Diseases (F32 AI138392)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- TMPRSS2, TMPRSS4, SARS-CoV-2, COVID-19 pandemic, enterocytes, serine protease, viral entry, intestinal mucosa
- MeSH terms
- Betacoronavirus, Angiotensin-Converting Enzyme 2, SARS-CoV-2, Animals, Cell Line, Duodenum, Humans, Peptidyl-Dipeptidase A, Membrane Proteins, Organoids, Rotavirus, Serine Endopeptidases, Vesiculovirus, Enterocytes, Mice, Virus Internalization
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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