Intranasally administrated fusion-inhibitory lipopeptides block SARS-CoV-2 infection in mice and enable long-term protective immunity

• DOI: 10.1038/s42003-025-07491-4
• Publication Date: 2025-01-15T14:52:33Z
• Authors: 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. Lieb...; Guillaume Noel; Cyrille Mathieu; Bernard Malissen; Thomas Briese; Alexander L. Gren...; Christopher A. Alabi; N. Valerio Dorrello; Stéphane Marot; Anne-Geneviève Ma...; Ana Zarubica; Anne Moscona; Matteo Porotto; Branka Horvat
• Keywords: QH301-705.5; [SDV]Life Sciences [q-bio]; 616; [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology; 610; Biology (General); Article

Abstract We have assessed antiviral activity and induction of protective immunity fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The block infection cell lines lung-derived organotypic cultures. Intranasal administration allows maintenance homeostatic transcriptomic immune profile lungs, prevents body-weight loss, decreases viral load shedding, protects death caused by variants. Prolonged high-dose has neither adverse effects nor impairs peptide efficacy subsequent challenges. peptide-protected develop cross-reactive neutralizing antibodies against both used for initial recently circulating variants, are completely protected a second lethal infection, suggesting that they developed SARS-CoV-2-specific immunity. This strategy provides an additional approach global effort COVID-19 may contribute to development rapid responses emerging pathogenic viruses.