Anti‐dengue virus serotype 2 activity and mode of action of a novel peptide

• Published in: Journal of applied microbiology 2015-10, Vol.119 (4), p.1170-1180
• Main Authors: Chew, M.‐F., Tham, H.‐W., Rajik, M., Sharifah, S.H.
• Format: Article
• Language: English
• Subjects: Animals; antiviral; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antiviral drugs; Cercopithecus aethiops; Dengue - virology; Dengue fever; Dengue virus; Dengue Virus - classification; Dengue Virus - drug effects; Dengue Virus - isolation & purification; Dengue Virus - physiology; drug; Humans; Molecular Sequence Data; peptide; Peptides; Peptides - chemistry; Peptides - pharmacology; phage; Pharmacology; Serogroup; Vero Cells; Viral Plaque Assay; Virus Replication - drug effects
• ISSN: 1364-5072; 1365-2672
• DOI: 10.1111/jam.12921

Aim To identify a novel antiviral peptide against dengue virus serotype 2 (DENV‐2) by screening a phage display peptide library and to evaluate its in vitro antiviral activity and mode of action. Methods and Results A phage display peptide library was biopanned against purified DENV‐2 and resulted in the identification and selection of a peptide (peptide gg‐ww) for further investigation. ELISA was performed, and peptide gg‐ww was shown to possess the highest binding affinity against DENV‐2. Thus, peptide gg‐ww was synthesized for cytotoxicity and antiviral assays. Virus plaque reduction assay, real‐time PCR and immunofluorescence assay were used to investigate the inhibitory effect of peptide gg‐ww on DENV‐2 infection in Vero cells. Three different assays (pre‐, simultaneous and post‐treatments assays) were performed to investigate the peptide's mode of action. Results indicated that peptide gg‐ww possessed strong antiviral activity with a ~96% inhibition rate, which was achieved at 250 μmol l−1. Viral replication was inhibited during a simultaneous treatment assay, indicating that the entry of the virus was impeded by this peptide. Conclusions Peptide gg‐ww displayed antiviral action against DENV‐2 by targeting an early stage of viral replication (i.e. during viral entry). Significance and Impact of the Study Peptide gg‐ww may represent a new therapeutic candidate for the treatment of DENV infections and is a potential candidate to be developed as a peptide drug.