Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production
| Autor: | Sansanee Noisakran, Pa-thai Yenchitsomanus, Prida Malasit, Pucharee Songprakhon, Chatchawan Srisawat, Chunya Puttikhunt, Chairat Uthaipibull, Prasit Luangaram, Thawornchai Limjindaporn, Sissades Thongsima, Thanawat Thaingtamtanha, Thanyaporn Dechtawewat |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Viral nonstructural protein viruses 030106 microbiology lcsh:Medicine Biopanning Viral Nonstructural Proteins Biology Dengue virus Virus Replication medicine.disease_cause Microbiology Antiviral Agents Article Virus Dengue fever Dengue 03 medical and health sciences Drug Delivery Systems Peptide Library Viral entry Virology Cell Line Tumor medicine Humans lcsh:Science Peptide library Multidisciplinary lcsh:R virus diseases Dengue Virus biochemical phenomena metabolism and nutrition medicine.disease 030104 developmental biology lcsh:Q Fluorescent tag |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-69515-9 |
| Popis: | Viruses manipulate the life cycle in host cells via the use of viral properties and host machineries. Development of antiviral peptides against dengue virus (DENV) infection has previously been concentrated on blocking the actions of viral structural proteins and enzymes in virus entry and viral RNA processing in host cells. In this study, we proposed DENV NS1, which is a multifunctional non-structural protein indispensable for virus production, as a new target for inhibition of DENV infection by specific peptides. We performed biopanning assays using a phage-displayed peptide library and identified 11 different sequences of 12-mer peptides binding to DENV NS1. In silico analyses of peptide-protein interactions revealed 4 peptides most likely to bind to DENV NS1 at specific positions and their association was analysed by surface plasmon resonance. Treatment of Huh7 cells with these 4 peptides conjugated with N-terminal fluorescent tag and C-terminal cell penetrating tag at varying time-of-addition post-DENV infection could inhibit the production of DENV-2 in a time- and dose-dependent manner. The inhibitory effects of the peptides were also observed in other virus serotypes (DENV-1 and DENV-4), but not in DENV-3. These findings indicate the potential application of peptides targeting DENV NS1 as antiviral agents against DENV infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|