Peptides developed against receptor binding sites of the E glycoprotein neutralize tick-borne encephalitis virus

Abstract Infection caused by tick-borne encephalitis virus (TBEV) often manifests with meningitis or encephalitis. Domain III (DIII) of the envelope (E) glycoprotein on the TBEV surface facilitates virion attachment to the cell receptor and initiates cell entry. As a result, this research focused on...

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Main Authors: Patrícia Petroušková, Katarína Bhide, Evelína Mochnáčová, Amod Kulkarni, Jana Jozefiaková, Zuzana Tkáčová, Tomáš Maľarik, Katarína Kucková, Lea Talpašová, Jakub Víglaský, Ádám Kevély, Kamila Koči, Eva Nováková, Juraj Koči, Mangesh Bhide
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-95449-1
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Summary:Abstract Infection caused by tick-borne encephalitis virus (TBEV) often manifests with meningitis or encephalitis. Domain III (DIII) of the envelope (E) glycoprotein on the TBEV surface facilitates virion attachment to the cell receptor and initiates cell entry. As a result, this research focused on the DIII to develop antiviral molecules that could prevent cell entry. We first identified two receptor-binding sites (RBS, 300SGLTYTMCDK309 and 317APTDSGHDTVVMEVTFSGTKPCR339) on DIII, that are involved in binding to human brain microvascular endothelial cells (hBMECs). Then we sought to isolate peptides from two combinatorial peptide-phage libraries that bind to the RBS and prevent protein E from attaching to hBMECs. Three cyclic peptides (CP2-CNSSKLHMC, CP20-CDGRPDRAC, CP23-CMKESIRGC) and a linear peptide (LP16-AFHPRQMETQMY) inhibited DIII binding to hBMECs. CP2 and CP20, both non-cytotoxic and hemocompatible, effectively neutralized a live virus. CP2 and CP20 deserve further attention for their potential application as anti-TBEV therapeutics that prevent viral cell entry.
ISSN:2045-2322