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 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

SUBMITTER: Mougari S 

PROVIDER: S-EPMC11735783 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature