Lethality due to dengue infection is a global threat. Nearly 400 million people are affected every year, which approximately costs 500 million dollars for surveillance and vector control itself. Many investigations on the structure-function relationship of proteins expressed by the dengue virus are being made for more than a decade and had come up with many reports on small molecule drug discov-ery. In this review, we present a detailed note on viral proteins and their functions as well as the inhibi-tors discovered/designed so far using experimental and computational methods. Further, the phytocon-stituents from medicinal plants, specifically the extract of the papaya leaves, neem and bael, which com-bat dengue infection via dengue protease, helicase, methyl transferase and polymerase are summarized. © 2020 Elsevier B.V., All rights reserved.