Abstract

BackgroundDengue continues to be a major international public health concern. Despite that, there is no clinically approved antiviral for treatment of dengue virus (DENV) infections. In this study, geraniin extracted from the rind of Nephelium lappaceum was shown to inhibit the replication of DENV-2 in both in vitro and in vivo experiments.MethodsThe effect of geraniin on DENV-2 RNA synthesis in infected Vero cells was tested using quantitative RT-PCR. The in vivo efficacy of geraniin in inhibiting DENV-2 infection was then tested using BALB/c mice with geraniin administered at three different times. The differences in spleen to body weight ratio, DENV-2 RNA load and liver damage between the three treatment groups as compared to DENV-2 infected mice without geraniin administration were determined on day eight post-infection.ResultsQuantitative RT-PCR confirmed the decrease in viral RNA synthesis of infected Vero cells when treated with geraniin. Geraniin seemed to provide a protective effect on infected BALB/c mice liver when given at 24 h pre- and 24 h post-infection as liver damage was observed to be very mild even though a significant reduction of DENV-2 RNA load in serum was not observed in these two treatment groups. However, when administered at 72 h post-infection, severe liver damage in the form of necrosis and haemorrhage had prevailed despite a substantial reduction of DENV-2 RNA load in serum.ConclusionsGeraniin was found to be effective in reducing DENV-2 RNA load when administered at 72 h post-infection while earlier administration could prevent severe liver damage caused by DENV-2 infection. These results provide evidence that geraniin is a potential candidate for the development of anti-dengue drug.

Highlights

  • Dengue continues to be a major international public health concern

  • The presence of dengue virus (DENV)-2 was confirmed when viral antigens were detected in focal areas of the damaged liver, making it an ideal model to investigate the pathogenesis of dengue disease and the anti-dengue potentials of natural compounds

  • This study investigates the prophylactic ability of geraniin, as well as its therapeutic effect on Dengue virus type-2 (DENV-2) infected BALB/c mice

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Summary

Introduction

Dengue continues to be a major international public health concern. Despite that, there is no clinically approved antiviral for treatment of dengue virus (DENV) infections. The absence of an appropriate animal model that can depict the true nature of the complex dengue pathogenesis has contributed to our lack of understanding of its pathogenesis, which is crucial in the process of developing any vaccines or antivirals [5] This absence has hindered research on dengue, especially on how the viral and host factors contributed to the severe forms of this. Paes and co-workers [8] had tested the feasibility of 8 weeks old male BALB/c mice as an experimental model in the study of dengue disease They reported that DENV-2 infected BALB/c mice developed an apparently mild infection, but histopathological and biochemical findings revealed liver injury. The presence of DENV-2 was confirmed when viral antigens were detected in focal areas of the damaged liver, making it an ideal model to investigate the pathogenesis of dengue disease and the anti-dengue potentials of natural compounds

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