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Delving into dengue virus drug discovery- insights into the structural characteristics of the RNA-dependent RNA polymerase.

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2017

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A precipitous increase in the number of flaviviral infections has been noted over the last five years. The present study sought to investigate a notorious flavivirus that has been in circulation for over 30 years. Over the last few decades, DENV has re-emerged in various serotypes and is causing mayhem in the lives of many. Dengue is dreaded for the severe fever it causes in its advanced stage. Dengue has the reputation of what is known as Dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue remains an unmet medical need that demands prompt attention. There remains no cure or preventative therapy due to the intransigence nature of this flavivirus. Its tenacity to resist antiviral therapy has left the scientific community with the burden of finding new and accelerated techniques to curb this virus. The onus is on scientists to probe further into understanding the Dengue virus by the use of cheminformatics and bioinformatics tools in the pursuit for an inhibitor against this pernicious virus. Of the Dengue structural and non-structural enzymes, the NS5 RNA-dependent RNA polymerase has been established as a promising target due to its conserved structure amongst all serotypes and its lack of an enzymatic counterpart in mammalian cells. Attempts have been made to design vaccines and small drug molecules as potential inhibitors against DENV. The virus however is resilient, and exists in 5 serotypes with numerous strains under them, thwarting the efforts of researchers to curb its spread. This prompted us to design a study that would address the above challenges by use of CADD tools, which elaborated on the design of target-specific inhibitors of DENV from an atomistic perspective. This included a pharmacophoric approach, which utilized computational software to map out a pharmacophore model against multiple flaviviruses, as well as a focused review on DENV serotype 2 and 3, which included a route map toward the design of target-specific DENV RdRp inhibitors. We believe that these findings will aid in mitigating the effects of the DENV in the lives of compromised individuals, as well as prevent the transmission of DENV from patients to healthy individuals.

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Masters Degrees (Pharmaceutical Sciences). University of KwaZulu-Natal. Westville, 2017.

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