In vitro evaluation of anti-dengue activity of selected synthetic schiff bases and traditional chinese medicinal plants extracts

During the last few decades, dengue virus (DENV) has emerged as the major virus spread by mosquito that can cause life threatening disease. Recently, it has spread to more than a hundred countries around the globe and still lacks a specific treatable medication. Hospitals provide only supportive and symptomatic treatment hence the development of a safe and effective antiviral is an urgent need. To identify new antivirals against DENV, realms of both synthetic compounds and ethnomedicine were explored. A library of eighty-five dithiocarbazate (DTC)-derived Schiff bases and their metal complexes including twelve plant extracts were analyzed in a primary antiviral evaluation. Hits displaying 50% or more anti-dengue activity were selected and evaluated through foci forming unit reduction assay, serotype based analysis and real time quantitative RT-PCR based time-of-addition analysis. During antiviral evaluation of synthetic compounds, ten anti-dengue compounds were identified with promising antiviral activity. Secondary evaluation presented two lead Ni complexes with SI values 86.3 and 80.4. Ni complexes were the strongest contestants and inhibited all DENV serotypes equally. Lead compounds inhibited against all stages of virus replication cycle but the activity was strongest during early stages. It was demonstrated in silico that Ni complexes were binding at domain III of DENV E-glycoprotein involved during early stages of replication. In conclusion, Schiff bases and their metal complexes are a whole new horizon for anti- dengue development and can be tudied further to develop safe, effective, stable, and affordable anti-dengue in future. Discovery and development of modern medicine relies on long and rigorous clinical trials until they are available for public use. Meanwhile, new classes of chemical compounds are being explored for innovative anti-dengue options, Traditional Chinese Medicinal (TCM) plants are frequently being used by dengue endemic populations as Contemporary and Alternate Medicine (CAM). These traditional herbs will continue to be an alternative for dengue treatment as disease burden is rapidly increasing every year. Present study also evaluated the anti-dengue potential of twelve TCM plant extracts designated as cool herbs used for the diseases with high fever. During antiviral evaluation of TCM plants, four anti-dengue plants were identified. Secondary evaluation proved two lead plants extract Dryopteris crassirhizoma (DC) and Morus alba (MA) with SI = 4.21 and 4.62 respectively, which inhibited DENV serotypes equally. In general, the plants were not equally inhibiting against all stages of viral replication cycle. DC was identified as potential anti-dengue plant which was active at late stages of virus replication. MA was also inhibiting but the dose was high, however its safety profile was better than DC and the plant was active at early stages of viral replication. Our research elucidated and identified the anti-dengue activity of the TCM plants in practice that have been time-tested to reduce the illness. Similar research can be planned for other traditional anti-dengue practices. The present times of integrated treatments brings together conventional medicine with safe and effective complementary medicine. Combined research approaches from different healthcare disciplines may lead to identification of new therapeutic options.

Text FPSK(p) 2019 39 - IR.pdf Download (1MB)

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