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Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production.

ABSTRACT: 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.

SUBMITTER: Songprakhon P

PROVIDER: S-EPMC7395749 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production.

Songprakhon Pucharee P Thaingtamtanha Thanawat T Limjindaporn Thawornchai T Puttikhunt Chunya C Srisawat Chatchawan C Luangaram Prasit P Dechtawewat Thanyaporn T Uthaipibull Chairat C Thongsima Sissades S Yenchitsomanus Pa-Thai PT Malasit Prida P Noisakran Sansanee S

Scientific reports 20200731 1

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 b ...[more]

PMID: 32737386

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Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production.

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Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production.

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