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

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

Publication date: Jan 15, 2025

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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Concepts Keywords
Antiviral Administration
Homeostatic Antiviral
Lungs Block
Transcriptomic Cov
Viral Derived
Fusion
Immunity
Infection
Inhibitory
Lipopeptides
Peptide
Protected
Protective
Sars
Variants

Semantics

Type Source Name
disease MESH SARS-CoV-2 infection
pathway REACTOME SARS-CoV-2 Infection
disease IDO cell
disease MESH weight loss
disease MESH viral load
disease MESH death
disease MESH infection
disease IDO host
disease IDO protein
disease IDO process
drug DRUGBANK Enfuvirtide
disease MESH syndrome
drug DRUGBANK Polyethylene glycol
drug DRUGBANK Cholesterol
disease IDO replication
disease MESH SD1
disease IDO assay
disease MESH measles
pathway KEGG Measles
drug DRUGBANK Neon
pathway KEGG Viral replication
drug DRUGBANK Proline
drug DRUGBANK Amino acids
disease MESH immune disorders
disease MESH reinfection
disease MESH virus infection
drug DRUGBANK L-Leucine
disease MESH Delta infection
drug DRUGBANK Topiramate
drug DRUGBANK Dimethyl sulfoxide
disease MESH encephalitis
disease IDO production
drug DRUGBANK Trestolone
disease MESH parainfluenza
pathway REACTOME Immune System
disease MESH emergency
drug DRUGBANK Glutamic Acid
drug DRUGBANK Benzylpenicillin
drug DRUGBANK Streptomycin
drug DRUGBANK (S)-Des-Me-Ampa
drug DRUGBANK Carboxymethylcellulose
drug DRUGBANK Gentian violet cation
drug DRUGBANK Dextrose unspecified form
drug DRUGBANK Sodium lauryl sulfate
disease MESH morbidity
disease MESH posture
disease IDO intervention
drug DRUGBANK Isoflurane
drug DRUGBANK Ketamine
drug DRUGBANK Xylazine
drug DRUGBANK Water
disease IDO blood
disease MESH bleeding
drug DRUGBANK Carbonate ion
drug DRUGBANK Biotin
drug DRUGBANK Platinum
drug DRUGBANK Sucrose
drug DRUGBANK Rifampicin
disease IDO infectivity
disease IDO reagent
drug DRUGBANK Trypsin
disease IDO facility
drug DRUGBANK Hydroxychloroquine
drug DRUGBANK Roxithromycin
disease MESH middle east respiratory syndrome
disease IDO susceptibility
disease MESH deletion mutations
disease MESH lung inflammation
disease MESH Nipah virus infection
disease MESH AIDS
disease MESH anosmia
disease IDO immunodeficiency
drug DRUGBANK Coenzyme M
pathway REACTOME Reproduction
disease IDO pathogen

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