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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-95449-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849734877868457984 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Patrícia Petroušková |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3e2995a42ff24cd4844286a4e5d0cd78 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-3e2995a42ff24cd4844286a4e5d0cd782025-08-20T03:07:41ZengNature PortfolioScientific Reports2045-23222025-04-0115111510.1038/s41598-025-95449-1Peptides developed against receptor binding sites of the E glycoprotein neutralize tick-borne encephalitis virusPatrícia Petroušková0Katarína Bhide1Evelína Mochnáčová2Amod Kulkarni3Jana Jozefiaková4Zuzana Tkáčová5Tomáš Maľarik6Katarína Kucková7Lea Talpašová8Jakub Víglaský9Ádám Kevély10Kamila Koči11Eva Nováková12Juraj Koči13Mangesh Bhide14Laboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceLaboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceLaboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceLaboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceLaboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceLaboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceLaboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceLaboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceLaboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceLaboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceDepartment of Virus Ecology, Institute of Virology, Biomedical Research Center, Slovak Academy of SciencesDepartment of Microbiology and Virology, Faculty of Natural Sciences, Comenius UniversityDepartment of Virus Ecology, Institute of Virology, Biomedical Research Center, Slovak Academy of SciencesDepartment of Virus Ecology, Institute of Virology, Biomedical Research Center, Slovak Academy of SciencesLaboratory of Biomedical Microbiology and Immunology, The University of Veterinary Medicine and Pharmacy in KošiceAbstract 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.https://doi.org/10.1038/s41598-025-95449-1Tick-borne encephalitis virusDomain IIIBlocking peptidesPhage displayhBMECsPRNT |
| spellingShingle | 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 Peptides developed against receptor binding sites of the E glycoprotein neutralize tick-borne encephalitis virus Scientific Reports Tick-borne encephalitis virus Domain III Blocking peptides Phage display hBMECs PRNT |
| title | Peptides developed against receptor binding sites of the E glycoprotein neutralize tick-borne encephalitis virus |
| title_full | Peptides developed against receptor binding sites of the E glycoprotein neutralize tick-borne encephalitis virus |
| title_fullStr | Peptides developed against receptor binding sites of the E glycoprotein neutralize tick-borne encephalitis virus |
| title_full_unstemmed | Peptides developed against receptor binding sites of the E glycoprotein neutralize tick-borne encephalitis virus |
| title_short | Peptides developed against receptor binding sites of the E glycoprotein neutralize tick-borne encephalitis virus |
| title_sort | peptides developed against receptor binding sites of the e glycoprotein neutralize tick borne encephalitis virus |
| topic | Tick-borne encephalitis virus Domain III Blocking peptides Phage display hBMECs PRNT |
| url | https://doi.org/10.1038/s41598-025-95449-1 |
| work_keys_str_mv | AT patriciapetrouskova peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT katarinabhide peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT evelinamochnacova peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT amodkulkarni peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT janajozefiakova peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT zuzanatkacova peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT tomasmalarik peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT katarinakuckova peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT leatalpasova peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT jakubviglasky peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT adamkevely peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT kamilakoci peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT evanovakova peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT jurajkoci peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus AT mangeshbhide peptidesdevelopedagainstreceptorbindingsitesoftheeglycoproteinneutralizetickborneencephalitisvirus |