Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication

Background: 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 lappac...

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Main Authors: Siti Aisyah Abdul Ahmad, Uma D.Palanisamy, Tejo, Bimo A., Chew, Miaw Fang *, Tham, Hong-Wai, Sharifah Syed Hassan
Format: Article
Language:English
Published: BioMed Central 2017
Subjects:
Online Access:http://eprints.sunway.edu.my/690/
http://eprints.sunway.edu.my/690/1/Chew%20Miaw%20Fang%20Geraniin%20extracted%20from%20the%20rind.pdf
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author Siti Aisyah Abdul Ahmad,
Uma D.Palanisamy,
Tejo, Bimo A.
Chew, Miaw Fang *
Tham, Hong-Wai
Sharifah Syed Hassan,
author_facet Siti Aisyah Abdul Ahmad,
Uma D.Palanisamy,
Tejo, Bimo A.
Chew, Miaw Fang *
Tham, Hong-Wai
Sharifah Syed Hassan,
author_sort Siti Aisyah Abdul Ahmad,
building SU Institutional Repository
collection Online Access
description Background: 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. Methods: Geraniin 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. Results: Cytotoxicity 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. Conclusions: Geraniin 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.
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spelling sunway-6902019-05-10T09:01:36Z http://eprints.sunway.edu.my/690/ Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication Siti Aisyah Abdul Ahmad, Uma D.Palanisamy, Tejo, Bimo A. Chew, Miaw Fang * Tham, Hong-Wai Sharifah Syed Hassan, QH301 Biology QR355 Virology Background: 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. Methods: Geraniin 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. Results: Cytotoxicity 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. Conclusions: Geraniin 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. BioMed Central 2017 Article PeerReviewed text en http://eprints.sunway.edu.my/690/1/Chew%20Miaw%20Fang%20Geraniin%20extracted%20from%20the%20rind.pdf Siti Aisyah Abdul Ahmad, and Uma D.Palanisamy, and Tejo, Bimo A. and Chew, Miaw Fang * and Tham, Hong-Wai and Sharifah Syed Hassan, (2017) Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication. Virology Journal, 14 (1). p. 229. ISSN 1743-422X http://dx.doi.org/10.1186/s12985-017-0895-1 doi:10.1186/s12985-017-0895-1
spellingShingle QH301 Biology
QR355 Virology
Siti Aisyah Abdul Ahmad,
Uma D.Palanisamy,
Tejo, Bimo A.
Chew, Miaw Fang *
Tham, Hong-Wai
Sharifah Syed Hassan,
Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication
title Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication
title_full Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication
title_fullStr Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication
title_full_unstemmed Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication
title_short Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication
title_sort geraniin extracted from the rind of nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication
topic QH301 Biology
QR355 Virology
url http://eprints.sunway.edu.my/690/
http://eprints.sunway.edu.my/690/
http://eprints.sunway.edu.my/690/
http://eprints.sunway.edu.my/690/1/Chew%20Miaw%20Fang%20Geraniin%20extracted%20from%20the%20rind.pdf