tetano
Editor, Senior Moderator
Commun Biol
. 2025 Jan 15;8(1):57.
doi: 10.1038/s42003-025-07491-4. Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity
Said Mougari[SUP] #[/SUP][SUP] 1 [/SUP], Valérie Favède[SUP] #[/SUP][SUP] 1 2 [/SUP], Camilla Predella[SUP] #[/SUP][SUP] 3 4 [/SUP], Olivier Reynard[SUP] 1 [/SUP], Stephanie Durand[SUP] 1 [/SUP], Magalie Mazelier[SUP] 1 [/SUP], Edoardo Pizzioli[SUP] 1 [/SUP], Didier Decimo[SUP] 1 [/SUP], Francesca T Bovier[SUP] 3 [/SUP], Lauren M Lapsley[SUP] 3 [/SUP], Candace Castagna[SUP] 5 [/SUP], Nicole A P Lieberman[SUP] 6 [/SUP], Guillaume Noel[SUP] 7 [/SUP], Cyrille Mathieu[SUP] 1 [/SUP], Bernard Malissen[SUP] 8 [/SUP], Thomas Briese[SUP] 9 [/SUP], Alexander L Greninger[SUP] 6 [/SUP], Christopher A Alabi[SUP] 10 [/SUP], N Valerio Dorrello[SUP] 3 [/SUP], Stéphane Marot[SUP] 11 [/SUP], Anne-Geneviève Marcelin[SUP] 11 [/SUP], Ana Zarubica[SUP] 8 [/SUP], Anne Moscona[SUP] 3 12 13 [/SUP], Matteo Porotto[SUP] 14 15 16 [/SUP], Branka Horvat[SUP] 17 [/SUP]
Affiliations
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.
. 2025 Jan 15;8(1):57.
doi: 10.1038/s42003-025-07491-4. Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity
Said Mougari[SUP] #[/SUP][SUP] 1 [/SUP], Valérie Favède[SUP] #[/SUP][SUP] 1 2 [/SUP], Camilla Predella[SUP] #[/SUP][SUP] 3 4 [/SUP], Olivier Reynard[SUP] 1 [/SUP], Stephanie Durand[SUP] 1 [/SUP], Magalie Mazelier[SUP] 1 [/SUP], Edoardo Pizzioli[SUP] 1 [/SUP], Didier Decimo[SUP] 1 [/SUP], Francesca T Bovier[SUP] 3 [/SUP], Lauren M Lapsley[SUP] 3 [/SUP], Candace Castagna[SUP] 5 [/SUP], Nicole A P Lieberman[SUP] 6 [/SUP], Guillaume Noel[SUP] 7 [/SUP], Cyrille Mathieu[SUP] 1 [/SUP], Bernard Malissen[SUP] 8 [/SUP], Thomas Briese[SUP] 9 [/SUP], Alexander L Greninger[SUP] 6 [/SUP], Christopher A Alabi[SUP] 10 [/SUP], N Valerio Dorrello[SUP] 3 [/SUP], Stéphane Marot[SUP] 11 [/SUP], Anne-Geneviève Marcelin[SUP] 11 [/SUP], Ana Zarubica[SUP] 8 [/SUP], Anne Moscona[SUP] 3 12 13 [/SUP], Matteo Porotto[SUP] 14 15 16 [/SUP], Branka Horvat[SUP] 17 [/SUP]
Affiliations
- PMID: 39814955
- DOI: 10.1038/s42003-025-07491-4
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.