Peptides as Therapeutic Agents for Dengue Virus

Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

Although studies demonstrated that DENV mainly enters host cells via receptor initiated-clathrin mediated endocytosis [102] [103] [104] , viral entry via clathrin-independent endocytic route has also been observed [104] . In addition, evidence of direct entry via fusion with plasmatic membrane leading to direct penetration into cytoplasm without undergoing endocytosis has also been described [105, 106] . Furthermore, evidence showed that DENV is able to infect a variety of cell types, including those isolated from humans [107, 108] , monkeys [92, 93] , hamsters [95, 109] and mosquitoes [110, 111] via different receptors. Therefore, the DENV entry pathway is greatly dependent on the cell type and viral strain. Due to the variability in viral entry routes and broad tissue tropism, targeting the viral structural proteins is easier than the vastly different cellular receptors, as DENV possesses the capability to utilize a wide range of cellular receptors and pathways to enter host cells. Viral structural proteins, especially the E protein, is therefore a popular target for antiviral inhibitors to interfere with the virus-host interactions and stop subsequent viral entry.