Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity
Abstract We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in c...
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07491-4 |
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| author | Said Mougari Valérie Favède Camilla Predella Olivier Reynard Stephanie Durand Magalie Mazelier Edoardo Pizzioli Didier Decimo Francesca T. Bovier Lauren M. Lapsley Candace Castagna Nicole A. P. Lieberman Guillaume Noel Cyrille Mathieu Bernard Malissen Thomas Briese Alexander L. Greninger Christopher A. Alabi N. Valerio Dorrello Stéphane Marot Anne-Geneviève Marcelin Ana Zarubica Anne Moscona Matteo Porotto Branka Horvat |
| author_facet | Said Mougari Valérie Favède Camilla Predella Olivier Reynard Stephanie Durand Magalie Mazelier Edoardo Pizzioli Didier Decimo Francesca T. Bovier Lauren M. Lapsley Candace Castagna Nicole A. P. Lieberman Guillaume Noel Cyrille Mathieu Bernard Malissen Thomas Briese Alexander L. Greninger Christopher A. Alabi N. Valerio Dorrello Stéphane Marot Anne-Geneviève Marcelin Ana Zarubica Anne Moscona Matteo Porotto Branka Horvat |
| author_sort | Said Mougari |
| collection | DOAJ |
| description | Abstract We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants. Prolonged administration of high-dose lipopeptides has neither adverse effects nor impairs peptide efficacy in subsequent SARS-CoV-2 challenges. The peptide-protected mice develop cross-reactive neutralizing antibodies against both SARS-CoV-2 used for the initial infection and recently circulating variants, and are completely protected from a second lethal infection, suggesting that they developed SARS-CoV-2-specific immunity. This strategy provides an additional antiviral approach in the global effort against COVID-19 and may contribute to development of rapid responses against emerging pathogenic viruses. |
| format | Article |
| id | doaj-art-17aff0803ee2427492f69dc4367f4169 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-17aff0803ee2427492f69dc4367f41692025-01-19T12:35:30ZengNature PortfolioCommunications Biology2399-36422025-01-018111610.1038/s42003-025-07491-4Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunitySaid Mougari0Valérie Favède1Camilla Predella2Olivier Reynard3Stephanie Durand4Magalie Mazelier5Edoardo Pizzioli6Didier Decimo7Francesca T. Bovier8Lauren M. Lapsley9Candace Castagna10Nicole A. P. Lieberman11Guillaume Noel12Cyrille Mathieu13Bernard Malissen14Thomas Briese15Alexander L. Greninger16Christopher A. Alabi17N. Valerio Dorrello18Stéphane Marot19Anne-Geneviève Marcelin20Ana Zarubica21Anne Moscona22Matteo Porotto23Branka Horvat24CIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de LyonCIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de LyonDivision of Pediatric Critical Care Medicine and Hospital Medicine, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterCIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de LyonCIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de LyonCIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de LyonCIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de LyonCIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de LyonDivision of Pediatric Critical Care Medicine and Hospital Medicine, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterDivision of Pediatric Critical Care Medicine and Hospital Medicine, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterInstitute of Comparative Medicine, Columbia University Irving Medical CenterDepartment of Laboratory Medicine and Pathology, University of Washington Medical CenterInstitut Claude Bourgelat, VetAgro Sup, Marcy l’EtoileCIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de LyonCentre d’Immunophénomique, Aix Marseille Université, Inserm, CNRS, PHENOMIN, CelphediaCenter for Infection and Immunity and Department of Epidemiology, Mailman School of Public Health, Columbia UniversityDepartment of Laboratory Medicine and Pathology, University of Washington Medical CenterRobert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell UniversityDivision of Pediatric Critical Care Medicine and Hospital Medicine, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterSorbonne Université, Virology department, Pitié-Salpêtrière hospital, AP-HP, Pierre Louis Epidemiology and Public Health instituteSorbonne Université, Virology department, Pitié-Salpêtrière hospital, AP-HP, Pierre Louis Epidemiology and Public Health instituteCentre d’Immunophénomique, Aix Marseille Université, Inserm, CNRS, PHENOMIN, CelphediaDivision of Pediatric Critical Care Medicine and Hospital Medicine, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterDivision of Pediatric Critical Care Medicine and Hospital Medicine, Department of Pediatrics, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterCIRI, Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de LyonAbstract We have assessed antiviral activity and induction of protective immunity of fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain of SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The lipopeptides block SARS-CoV-2 infection in cell lines and lung-derived organotypic cultures. Intranasal administration in mice allows the maintenance of homeostatic transcriptomic immune profile in lungs, prevents body-weight loss, decreases viral load and shedding, and protects mice from death caused by SARS-CoV-2 variants. Prolonged administration of high-dose lipopeptides has neither adverse effects nor impairs peptide efficacy in subsequent SARS-CoV-2 challenges. The peptide-protected mice develop cross-reactive neutralizing antibodies against both SARS-CoV-2 used for the initial infection and recently circulating variants, and are completely protected from a second lethal infection, suggesting that they developed SARS-CoV-2-specific immunity. This strategy provides an additional antiviral approach in the global effort against COVID-19 and may contribute to development of rapid responses against emerging pathogenic viruses.https://doi.org/10.1038/s42003-025-07491-4 |
| spellingShingle | Said Mougari Valérie Favède Camilla Predella Olivier Reynard Stephanie Durand Magalie Mazelier Edoardo Pizzioli Didier Decimo Francesca T. Bovier Lauren M. Lapsley Candace Castagna Nicole A. P. Lieberman Guillaume Noel Cyrille Mathieu Bernard Malissen Thomas Briese Alexander L. Greninger Christopher A. Alabi N. Valerio Dorrello Stéphane Marot Anne-Geneviève Marcelin Ana Zarubica Anne Moscona Matteo Porotto Branka Horvat Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity Communications Biology |
| title | Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity |
| title_full | Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity |
| title_fullStr | Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity |
| title_full_unstemmed | Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity |
| title_short | Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity |
| title_sort | intranasally administrated fusion inhibitory lipopeptides block sars cov 2 infection in mice and enable long term protective immunity |
| url | https://doi.org/10.1038/s42003-025-07491-4 |
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