biostudies-literatureKakizaki MMEXT | Japan Society for the Promotion of ScienceShionogi Infectious Disease Research Promotion FoundationMEXT | Japan Society for the Promotion of Science (JSPS)The Mitsubishi FoundationJapan Agency for Medical Research and DevelopmentAstellas Foundation for Research on Metabolic DisordersThe Chemo-Sero-Therapeutic Research InstituteJapan Agency for Medical Research and Development (AMED)e0185324https://www.ebi.ac.uk/biostudies/studies/S-EPMC11784140biostudies-literatureUnknown99(1)A critical aspect of the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the protease-mediated activation of the viral spike (S) protein. The type II transmembrane serine protease TMPRSS2 is crucial for SARS-CoV-2 infection in lung epithelial Calu-3 cells and murine airways. However, the importance of TMPRSS2 needs to be re-examined because the ability to utilize TMPRSS2 is significantly reduced in the Omicron variants that spread globally. For this purpose, replication profiles of SARS-CoV-2 were analyzed in human respiratory organoids. All tested viruses, including Omicron variants, replicated efficiently in these organoids. Notably, all SARS-CoV-2 strains retained replication ability in TMPRSS2-gene knockout (KO) respiratory organoids, suggesting tJournal of virologyThe respective roles of TMPRSS2 and cathepsins for SARS-CoV-2 infection in human respiratory organoids.PMC11784140JP243fa627001JP21gm161000523K0793523K17416JP23jf0126002JPJSCCA20240006Kakizaki MNagata NTakeda MOkura THashimoto RRyo AKitai YShirato KYamamoto TAkahori YKatoh HTakayama KfalseThe respective roles of TMPRSS2 and cathepsins for SARS-CoV-2 infection in human respiratory organoids.A critical aspect of the mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the protease-mediated activation of the viral spike (S) protein. The type II transmembrane serine protease TMPRSS2 is crucial for SARS-CoV-2 infection in lung epithelial Calu-3 cells and murine airways. However, the importance of TMPRSS2 needs to be re-examined because the ability to utilize TMPRSS2 is significantly reduced in the Omicron variants that spread globally. For this purpose, replication profiles of SARS-CoV-2 were analyzed in human respiratory organoids. All tested viruses, including Omicron variants, replicated efficiently in these organoids. Notably, all SARS-CoV-2 strains retained replication ability in TMPRSS2-gene knockout (KO) respiratory organoids, suggesting t2025-01-01T00:00:00Z2025 Jan2025-04-04T23:11:39.495Z2025-04-04T23:11:39.495ZS-EPMC117841403960159210.1128/jvi.01853-24