{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:03:49Z","timestamp":1791911029006,"version":"4.3.4"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"COVID-19 Research Network Lower Saxony (COFONI) in the Flex-Funds procedure \u201cCOFONI-PROTECT\u201d (6FF22)"},{"name":"Helmholtz Association\u2019s Initiative and Networking Fund"},{"name":"Peter and Traudl Engelhorn foundation"},{"name":"Hessian Ministry for Science and the Arts"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The COVID-19 pandemic remains a global health threat and novel antiviral strategies are urgently needed. SARS-CoV-2 employs the cellular serine protease TMPRSS2 for entry into lung cells, and TMPRSS2 inhibitors are being developed for COVID-19 therapy. However, the SARS-CoV-2 Omicron variant, which currently dominates the pandemic, prefers the endo\/lysosomal cysteine protease cathepsin L over TMPRSS2 for cell entry, raising doubts as to whether TMPRSS2 inhibitors would be suitable for the treatment of patients infected with the Omicron variant. Nevertheless, the contribution of TMPRSS2 to the spread of SARS-CoV-2 in the infected host is largely unclear. In this study, we show that the loss of TMPRSS2 strongly reduced the replication of the Beta variant in the nose, trachea and lung of C57BL\/6 mice, and protected the animals from weight loss and disease. The infection of mice with the Omicron variant did not cause disease, as expected, but again, TMPRSS2 was essential for efficient viral spread in the upper and lower respiratory tract. These results identify the key role of TMPRSS2 in SARS-CoV-2 Beta and Omicron infection, and highlight TMPRSS2 as an attractive target for antiviral intervention.<\/jats:p>","DOI":"10.3390\/v15020271","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T01:57:57Z","timestamp":1674007077000},"page":"271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["TMPRSS2 Is Essential for SARS-CoV-2 Beta and Omicron Infection"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0862-047X","authenticated-orcid":false,"given":"Kristin","family":"Metzdorf","sequence":"first","affiliation":[{"name":"Department of Viral Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7831-1330","authenticated-orcid":false,"given":"Henning","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"Department of Viral Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina C.","family":"Greweling-Pils","sequence":"additional","affiliation":[{"name":"Mouse-Pathology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4603-7696","authenticated-orcid":false,"given":"Markus","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Infection Biology Unit, German Primate Center, 37077 G\u00f6ttingen, Germany"},{"name":"Faculty of Biology and Psychology, Georg-August-University G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"L\u00fcddecke","sequence":"additional","affiliation":[{"name":"Department of Viral Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicitas","family":"Miller","sequence":"additional","affiliation":[{"name":"Mouse-Pathology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Melcher","sequence":"additional","affiliation":[{"name":"Immune Regulation Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy M.","family":"Kempf","sequence":"additional","affiliation":[{"name":"Infection Biology Unit, German Primate Center, 37077 G\u00f6ttingen, Germany"},{"name":"Faculty of Biology and Psychology, Georg-August-University 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Goethe University Frankfurt, 60596 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-7565","authenticated-orcid":false,"given":"Sandra","family":"Ciesek","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology, University Hospital, Goethe University Frankfurt, 60596 Frankfurt am Main, Germany"},{"name":"DZIF\u2014German Centre for Infection Research, External Partner Site, 60596 Frankfurt, Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), 60595 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6086-9136","authenticated-orcid":false,"given":"Stefan","family":"P\u00f6hlmann","sequence":"additional","affiliation":[{"name":"Infection Biology Unit, German Primate Center, 37077 G\u00f6ttingen, Germany"},{"name":"Faculty of Biology and Psychology, Georg-August-University G\u00f6ttingen, 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