Peptides as Therapeutic Agents for Dengue Virus

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

On the other hand, the DENV C protein (approximately 11 kDa) is composed of four α-helical regions arranged in antiparallel homodimers [147] . The structure of the C protein contains high net charge with an asymmetric distribution of basic residues which lie along the surface of the C protein to orchestrate RNA binding. In contrast, the opposite surface forms a hydrophobic region which may enable interactions with lipids [147, 148] . This configuration makes the C protein essential in virus assembly as it enables encapsulation of the ssRNA genome to form the nucleocapsid [45] . Despite a general understanding of the viral RNA assembly role, it is believed that the hydrophobic region of the C-terminal capsid protein contains a signal sequence for anchoring the protein into the endoplasmic reticulum (ER) membrane and partitioning the prM protein to the membrane [143, 149] . The C-terminal is then cleaved off by the viral NS2B-NS3 protease to form a mature protein during virus assembly [148] . Faustino et al. (2015) have designed a peptide inhibitor, pep14-23, based on the conserved region of DENV C protein. The pep14-23 was able to interfere with the interaction of the DENV C protein with the host intracellular lipid droplet, which was shown to be essential for viral particle formation [46, 150] . It was found that the binding forces between the C protein and lipid droplets were reduced from 33 pN to 19 pN with the addition of 100 µM pep14-23. Interestingly, despite the importance of the C protein for viral survival, limited antiviral peptide was designed against the C protein. This is a target worth looking into.