Peptides as Therapeutic Agents for Dengue Virus

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

The DC-SIGN is a type II transmembrane protein that falls into the category of C-type lectin with an extracellular domain that can bind specifically to carbohydrates [82] . DC-SIGN has been shown to be an essential cellular factor required for the infection of ebola virus [83, 84] , HIV-1 [85, 86] and human cytomegalovirus (CMV) [87] into dendritic cells. Studies have also shown that dendritic cells that abundantly express DC-SIGN are highly susceptible to DENV infection [33, 88, 89] . Tassaneetrithep et al. (2003) further validated the importance of DC-SIGN as a DENV receptor [34] , whereby the transfection of DC-SIGN into THP-1 cells resulted in DENV infection while dendritic cells blocked with anti-DC-SIGN prevented DENV infection [34] . These results suggest that DC-SIGN is a feasible target for designing therapies that prevent DENV infection. Furthermore, dendritic cells were activated after capturing antigen and resulted in the stimulation of naïve T cells to produce cytokines and chemokines [90] . Blocking the binding of DENV to DC-SIGN can prevent DENV infection, as well as the initiation of immune response which can lead to severe dengue characterized by the cytokine storm. Based on the literature, limited DC-SIGN inhibitors are found to stop DENV infection. In a study, Alen et al. (2011) evaluated the inhibitory properties of various carbohydrate-binding agents (CBAs) which are mannose-specific plant lectins by using the Raji/DC-SIGN+ cell line. Results showed that Hippeastrum hybrid (HHA), Galanthus nivalis (GNA) and Urtica dioica (UDA) were able to bind to the envelope of DENV, hence preventing the subsequent viral attachment [91] . Similarly, pradimicin-s (PRM-S), a small-size non-peptidic CBA, was shown to exert antiviral activity against DENV by binding to the DENV envelope in monocyte-derived dendritic cells [91] .