Petroušková et al.
Peptides developed against receptor-binding sites of the E glycoprotein neutralize tick-borne encephalitis virus. Sci Rep. 2025;15(1):11435. doi:10.1038/s41598-025-95449-1
Currently, no TBE-specific therapy is available. Therefore, the development of effective therapeutic molecules, such as antibodies (see e.g., Snapshot week 49/2023), peptides, or synthetic compounds (see e.g., Snapshot week 36/2024, Snapshot week 33/2023, Snapshot week 32/2023, and Snapshot week 2/2023), is highly desirable. One promising antiviral strategy is the inhibition of viral cell entry by blocking viral attachment proteins with peptides.
Attachment and entry of TBE virus are mediated by the envelope glycoprotein E (gE), which comprises three domains: D1, D2, and D3. Among these, D3 is the major antigenic domain and plays a critical role in receptor attachment, making it an attractive target for developing entry-inhibiting peptides that specifically bind to its receptor-binding sites.
Using combinatorial phage-display libraries, peptides with the potential to block viral cell entry were identified. These peptides were overexpressed in E. coli and had molecular masses between 1.352 and 1.797 kDa. Several were found to be target-specific, well-tolerated in cell culture, and capable of inhibiting virus entry in vitro (strain Hypr infecting BHK21 cells). Moreover, some peptides also blocked viral infection of brain microvascular endothelial cells. Notably, cyclic peptides showed stronger affinity for D3 and demonstrated superior TBEV neutralization compared to linear peptides.
Two cyclic peptide candidates—CP2 and CP20—exhibited no cytotoxicity or hemolytic activity, while completely neutralizing the TBE virus and fully preventing viral infection. These findings highlight their potential as promising anti-TBE therapeutics designed to block viral cell entry.