Abstract
BackgroundThe rapid rise and spread in dengue cases, together with the unavailability of safe vaccines and effective antiviral drugs, warrant the need to discover and develop novel anti-dengue treatments. In this study the antiviral activity of geraniin, extracted from the rind of Nephelium lappaceum, against dengue virus type-2 (DENV-2) was investigated.MethodsGeraniin was prepared from Nephelium lappaceum rind by reverse phase C-18 column chromatography. Cytotoxicity of geraniin towards Vero cells was evaluated using MTT assay while IC50 value was determined by plaque reduction assay. The mode-of-action of geraniin was characterized using the virucidal, attachment, penetration and the time-of-addition assays’. Docking experiments with geraniin molecule and the DENV envelope (E) protein was also performed. Finally, recombinant E Domain III (rE-DIII) protein was produced to physiologically test the binding of geraniin to DENV-2 E-DIII protein, through ELISA competitive binding assay.ResultsCytotoxicity assay confirmed that geraniin was not toxic to Vero cells, even at the highest concentration tested. The compound exhibited DENV-2 plaque formation inhibition, with an IC50 of 1.75 μM. We further revealed that geraniin reduced viral infectivity and inhibited DENV-2 from attaching to the cells but had little effect on its penetration. Geraniin was observed to be most effective when added at the early stage of DENV-2 infection. Docking experiments showed that geraniin binds to DENV E protein, specifically at the DIII region, while the ELISA competitive binding assay confirmed geraniin’s interaction with rE-DIII with high affinity.ConclusionsGeraniin from the rind of Nephelium lappaceum has antiviral activity against DENV-2. It is postulated that the compound inhibits viral attachment by binding to the E-DIII protein and interferes with the initial cell-virus interaction. Our results demonstrate that geraniin has the potential to be developed into an effective antiviral treatment, particularly for early phase dengue viral infection.
Highlights
The rapid rise and spread in dengue cases, together with the unavailability of safe vaccines and effective antiviral drugs, warrant the need to discover and develop novel anti-dengue treatments
Preparation of geraniin from Nephelium lappaceum L. rind by reverse phase C-18 column chromatography Nephelium lappaceum L. was obtained from Kuala Lumpur, Peninsular Malaysia and plants were authenticated by the Herbarium of the Forest Research Institute of Malaysia (FRIM)
It was observed that patients who are infected with dengue virus (DENV)-2 experienced more severe disease and had a higher chance of having dengue haemorrhagic fever (DHF) than those infected with other serotypes [35]
Summary
The rapid rise and spread in dengue cases, together with the unavailability of safe vaccines and effective antiviral drugs, warrant the need to discover and develop novel anti-dengue treatments. In this study the antiviral activity of geraniin, extracted from the rind of Nephelium lappaceum, against dengue virus type-2 (DENV-2) was investigated. The fast spread of dengue pandemic especially in tropical countries is worrisome. Dengue is caused by dengue virus (DENV), which belongs to the family Flaviviridae and the genus Flavivirus [2, 4]. DENV has four antigenically related serotypes named DENV-1, DENV-2, DENV-3, and DENV-4, each causing similar series of illnesses ranging from asymptomatic to a selflimiting febrile illness, to severe and fatal haemorrhagic disease [5]. DENV is mostly spread through its fundamental vector, the Aedes aegypti; which is bred in tropical urban areas packed with human. The major E protein, which forms the glycoprotein shell of the virus, consists of three β-barrel domains namely; Domain I, Domain II, and Domain III [8]. Domain I contains the Nterminus, Domain II mediates dimerization of E, while Domain III is predicted to be involved in receptor binding and antibody neutralization
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