Progress in Medicinal Chemistry for Neglected Tropical Diseases: A Focus on Denv Drug Discovery (2014-2023)

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Dengue is still a major concern as we are yet to identify a potent inhibitor, and unfortunately, there is loss of life associated with this disease; however, the fatalities are low, but every year, dengue is an added burden to the medical infrastructure. In a world hit by COVID-19 pandemic, dengue is yet another serious burden. To date, we do not have any approved medicine to combat this disease. Symptomatic treatment to reduce the fever and intensive care facilities for critical patients is the only treatment protocol adopted as of now. Earlier, it was a disease of tropical nations of the world, but now it has been observed that it has extended its reach beyond the tropical and subtropical nations. The WHO data suggest that the year 2023 saw a record over 5000 reported cases of death due to dengue in about 80 countries across the world. These data further call for the urgency in identifying inhibitors for dengue. In the book chapter, we have compiled the efforts made so far in the last decade to give a DENV inhibitor. Our extensive survey of the literature indicated that protease of DENV was the most explored target and besides these targets like NS5 methyltransferase, RdRp, and E proteins did report few molecules. The success of proteases for drug discovery in diseases like HIV and HCV has encouraged researchers to exploit the DENV proteases. In this book chapter, we identified varying scaffolds contributing to the inhibition of Dengue virus and by different mechanisms.