Efficacy of geraniin on dengue virus type-2 infected BALB/c mice

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RESEARCH

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Efficacy of geraniin on dengue virus type-2 infected BALB/c mice Siti Aisyah Abdul Ahmad1, Uma D. Palanisamy1, Joon Joon Khoo2, Amreeta Dhanoa1 and Sharifah Syed Hassan1,3*

Abstract Background: 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. 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. Methods: The 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. Results: Quantitative 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. Conclusions: Geraniin was found to be effective in reducing DENV-2 RNA load when administered at 72 h postinfection 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. Keywords: Antiviral, Dengue virus, Geraniin, In vivo

Background Dengue is a debilitating disease spread through the bite of an Aedes mosquito that carries DENV. The four serotypes of DENV (DENV-1, DENV-2, DENV-3 and DENV-4) belong to the genus Flavivirus and the family Flaviviridae [1]. DENV genome is made up of a single stranded positive-sense RNA which encodes three structural (capsid [C], membrane [M], and envelope [E]) and seven non-structural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins [2]. Infection with DENV causes a wide spectrum of clinical manifestations ranging from * Correspondence: [email protected] 1 Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia 3 Infectious Diseases and Health Cluster, Tropical Medicine and Biology Platform, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor, Malaysia Full list of author information is available at the end of the article

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