Inhibition of dengue virus entry into target cells using synthetic antiviral peptides

Alhoot, M.A. and Rathinam, A.K. and Wang, S.M. and Manikam, R. and Sekaran, S.D. (2013) Inhibition of dengue virus entry into target cells using synthetic antiviral peptides. International Journal of Medical Sciences, 10 (6). pp. 719-729. ISSN 1449-1907,

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Despite the importance of DENV as a human pathogen, there is no specific treatment or protective vaccine. Successful entry into the host cells is necessary for establishing the infection. Recently, the virus entry step has become an attractive therapeutic strategy because it represents a barrier to suppress the onset of the infection. Four putative antiviral peptides were designed to target domain III of DENV-2 E protein using BioMoDroid algorithm. Two peptides showed significant inhibition of DENV when simultaneously incubated as shown by plaque formation assay, RT-qPCR, and Western blot analysis. Both DET4 and DET2 showed significant inhibition of virus entry (84.6 and 40.6 respectively) using micromolar concentrations. Furthermore, the TEM images showed that the inhibitory peptides caused structural abnormalities and alteration of the arrangement of the viral E protein, which interferes with virus binding and entry. Inhibition of DENV entry during the initial stages of infection can potentially reduce the viremia in infected humans resulting in prevention of the progression of dengue fever to the severe life-threatening infection, reduce the infected vector numbers, and thus break the transmission cycle. Moreover these peptides though designed against the conserved region in DENV-2 would have the potential to be active against all the serotypes of dengue and might be considered as Hits to begin designing and developing of more potent analogous peptides that could constitute as promising therapeutic agents for attenuating dengue infection.

Item Type: Article
Additional Information: ISI Document Delivery No.: 134UN Times Cited: 2 Cited Reference Count: 42 Alhoot, Mohammed Abdelfatah Rathinam, Alwin Kumar Wang, Seok Mui Manikam, Rishya Sekaran, Shamala Devi High Impact Research Grant from University Malaya J-00000-73560, H-200001-00-E000079; University of Malaya IPPP Grant PV053/2011B This project was supported by High Impact Research Grant from University Malaya J-00000-73560, H-200001-00-E000079 and University of Malaya IPPP Grant: PV053/2011B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ivyspring int publ Lake haven
Uncontrolled Keywords: Dengue virus, Antiviral peptides, Inhibitory Peptides, Viral entry, Envelope protein, Domain III, herpes-simplex-virus, hepatitis-b-virus, protein-structure prediction, envelope protein, rna interference, heparan-sulfate, membrane-fusion, in-vitro, replication, binding
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms azrahani halim
Date Deposited: 05 Nov 2014 00:55
Last Modified: 05 Nov 2014 00:55

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