Branched peptide for antiviral use

Given that many viruses utilise heparan sulfate proteoglycans (HSPGs) as receptors or co-receptors on target cells, the present solution is a branched peptide with antiviral activity that binds to HSPG receptors on target cells.

Incorporating the already known and characterized anti-tumor peptide NT4 in a branched form, thus improving its stability and local bioavailability, the new antiviral peptide is specific for binding to sulfur-containing GAGs of HSPGs such as heparin, as confirmed by flow cytometric tests on various cell lines (Caco-2, MT-2, MT-4, PM-1, and H9). This binding directly competes with the virus for the same cellular receptors, thus inhibiting infection and viral internalisation while maintaining minimal cytotoxicity after 24 hours of exposure.

Specifically, the efficacy of the peptides has been evaluated in vitro for SARS-CoV-2 and HIV. In the former case, a significant reduction in infection of Caco-2 cells with the Omicron and Delta variants of SARS-CoV-2 was observed at peptide concentrations below 100 µM. In the latter case, a dose-dependent inhibition of MT-2 cell infection (expressing the CCR5 or CXCR4 co-receptor) by HIV was observed at peptide concentrations below 0.9 µM.

The peptides can be used in place of, or in combination with, existing antiviral drugs as part of an antiviral therapeutic regimen for HSPG-binding species (Adenovirus, Flavivirus, Herpes Virus, Alphavirus, Papillomavirus, HBV, Hepatitis Delta virus, HCV, Coronavirus, Lentivirus), including known resistant strains.