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

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Mougari, Said | Favède, Valérie | Predella, Camilla | Reynard, Olivier | Durand, Stephanie | Mazelier, Magalie | Pizzioli, Edoardo | Decimo, Didier | Bovier, Francesca | Lapsley, Lauren | Castagna, Candace | Lieberman, Nicole | Noel, Guillaume | Mathieu, Cyrille | Malissen, Bernard | Briese, Thomas | Greninger, Alexander | Alabi, Christopher | Dorrello, N. Valerio | Marot, Stéphane | Marcelin, Anne-Geneviève | Zarubica, Ana | Moscona, Anne | Porotto, Matteo | Horvat, Branka

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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