Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases
Summary: SARS-CoV-2 entry into host cells depends on proteolytic activation of the spike protein by host proteases, a process shaped by spike mutations that influence viral specificity and infectivity. Using human airway epithelial models, this study investigated how different SARS-CoV-2 variants in...
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| Language: | English |
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Elsevier
2025-09-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225015792 |
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| author | Aleksandra Milewska Luis Fernando Cofas-Vargas Adolfo B. Poma Krzysztof Pyrć |
| author_facet | Aleksandra Milewska Luis Fernando Cofas-Vargas Adolfo B. Poma Krzysztof Pyrć |
| author_sort | Aleksandra Milewska |
| collection | DOAJ |
| description | Summary: SARS-CoV-2 entry into host cells depends on proteolytic activation of the spike protein by host proteases, a process shaped by spike mutations that influence viral specificity and infectivity. Using human airway epithelial models, this study investigated how different SARS-CoV-2 variants interact with host serine proteases. The Delta variant exhibited enhanced and stable binding to Hepsin through stronger ionic and hydrophobic interactions, promoting efficient spike activation and cell entry. In contrast, Omicron BA.1 showed weaker Hepsin binding and relied more on TMPRSS2 or cathepsins, depending on the cellular context. These findings reveal how variant-specific differences in protease usage are linked to spike protein mutations and cleavage site evolution. By illuminating the dynamic interplay between viral adaptation and host protease specificity, this work provides insights into mechanisms that influence viral transmission and immune evasion, with implications for developing targeted antiviral strategies and understanding the evolution of emerging SARS-CoV-2 variants. |
| format | Article |
| id | doaj-art-6cf07e3d60fc4f4b9941c28c1d9ff404 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-6cf07e3d60fc4f4b9941c28c1d9ff4042025-08-22T04:57:10ZengElsevieriScience2589-00422025-09-0128911331810.1016/j.isci.2025.113318Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteasesAleksandra Milewska0Luis Fernando Cofas-Vargas1Adolfo B. Poma2Krzysztof Pyrć3Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30-387 Krakow, PolandInstitute of Fundamental Technological Research, Polish Academy of Sciences, Pawińskiego 5B, 02-106 Warsaw, PolandInstitute of Fundamental Technological Research, Polish Academy of Sciences, Pawińskiego 5B, 02-106 Warsaw, Poland; Corresponding authorVirogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7A, 30-387 Krakow, Poland; Corresponding authorSummary: SARS-CoV-2 entry into host cells depends on proteolytic activation of the spike protein by host proteases, a process shaped by spike mutations that influence viral specificity and infectivity. Using human airway epithelial models, this study investigated how different SARS-CoV-2 variants interact with host serine proteases. The Delta variant exhibited enhanced and stable binding to Hepsin through stronger ionic and hydrophobic interactions, promoting efficient spike activation and cell entry. In contrast, Omicron BA.1 showed weaker Hepsin binding and relied more on TMPRSS2 or cathepsins, depending on the cellular context. These findings reveal how variant-specific differences in protease usage are linked to spike protein mutations and cleavage site evolution. By illuminating the dynamic interplay between viral adaptation and host protease specificity, this work provides insights into mechanisms that influence viral transmission and immune evasion, with implications for developing targeted antiviral strategies and understanding the evolution of emerging SARS-CoV-2 variants.http://www.sciencedirect.com/science/article/pii/S2589004225015792Molecular interactionCell biologyBioinformatics |
| spellingShingle | Aleksandra Milewska Luis Fernando Cofas-Vargas Adolfo B. Poma Krzysztof Pyrć Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases iScience Molecular interaction Cell biology Bioinformatics |
| title | Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases |
| title_full | Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases |
| title_fullStr | Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases |
| title_full_unstemmed | Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases |
| title_short | Evolution of the SARS-CoV-2 spike protein in utilizing host transmembrane serine proteases |
| title_sort | evolution of the sars cov 2 spike protein in utilizing host transmembrane serine proteases |
| topic | Molecular interaction Cell biology Bioinformatics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225015792 |
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