Peptides as Therapeutic Agents for Dengue Virus

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

One of the attractive approaches to inhibiting virus infection is by blocking the cellular receptors or attachment factors, or mimicking the cellular receptors, hence preventing the virus from attaching and entering host cells. This will form the first barrier to block viral infection. Studies have shown that this is a feasible approach to halting viral infections [68] [69] [70] . Pugach et al. (2008) and Lieberman-Blum et al. (2008) demonstrated that a small molecule, CCR5 inhibitor, Maraviroc, successfully inhibited human immunodeficiency virus type 1 (HIV-1) infection by binding to the CCR5 co-receptor of host cells [68, 69] . On the other hand, Myrcludex B, a lipomyristolated peptide containing 47 homologous amino acid residues of hepatitis B virus pre-S1 protein, was able to bind to the NTCP of host cells and resulted in the restriction of virion uptake in the host cells [70] . [71, 72] . Some of the important attachment factors or receptors are the dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) [34] , heparan sulfate [73] , mannose receptor [74] , HSP90/HSP70 [75] , laminin receptor [76] , and the TIM and TAM proteins [77] . To date, several small molecules were identified as receptor antagonists or mimics for DENV. For instance, CC-chemokine receptor 5 (CCR5) antagonists, Met-R and UK484900 (a Maraviroc analogue) prevented CCR5 activation and reduced DENV load [78] , while heparin sulfate mimetics, such as PI-88 [79] , fucoidan [80] and CF-238 [81] , were shown to block viral entry. Interestingly, to the best of our knowledge, no peptide inhibitors were found to block DENV infection by binding to cellular attachment factors or receptors. This represents a big research gap that should prompt researchers to investigate.