In vitro and in silico Anti-dengue activity of Supercritical extract of medicinal plants against Dengue serotype-2

Abstract

Dengue is transmitted by female Aedes mosquitoes. It has been reported that about 2.5 billion peoples are at the risk of dengue virus. Millions of cases of dengue virus occur worldwide each year. There is no antiviral drug available still. Hence, the researchers are in the search of new anti-dengue drugs from natural products. The present study is aimed to determine the anti-dengue activity of supercritical extracts of Andrographis paniculata, Berberis vulgaris, Carica papaya, Euphorbia hirta, Phyllanthus niruri and Tinospora cordifolia in vitro and in silico. The cell viability was evaluated in C6/36 cells line by using MTT assay using a microplate reader at 595 nm. The maximum non-toxic dose of C. papaya and B. vulgaris extracts were reported as 46.87µg/ml, 31.25µg/ml for A. paniculata, P. niruri and E. hirta and 23.43 µg/ml, for T. cordifolia. Further, the anti-dengue activity of plants extract was analyzed by real-time RT-PCR. 100 copies/ml of DENV-2 virus was used for the antiviral assay. A. paniculata supercritical extract showed complete inhibition against the dengue-2 virus at 40ºC temperature and 15Mpa pressure. The other plant extracts showed the inhibition in order of T. cordifolia (83.44%) > C. papaya (34.71%) > E. hirta (28.70%) whereas P. niruri and B. vulgaris failed to inhibit dengue virus. Andrographolide a major compound present in A. paniculata has been reported to have antiviral activity against hepatitis B, C virus, herpes simplex virus, influenza virus, chikungunya virus, dengue virus 2 and 4. Results of molecular docking showed that the interaction between andrographolide and NS1protein shows the maximum binding energy -7.30 Kcal/mol. The docking study was conducted to validate the result against the anti-dengue activity using dengue NS1 protein with andrographolide. It was concluded that A. paniculata could be a source for isolation of therapeutic compounds against the dengue-2 virus.