Peptides as Therapeutic Agents for Dengue Virus

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

The viral infection cycle starts with the interaction of viral structural proteins, mediated mainly by the E protein with the host cell receptors or attachment factors to facilitate the entry of virus. The DENV E protein is 53 kDa in size and composed of three distinct domains, namely the domain I E(I), flanked by the dimerization domain E(II) containing the fusion peptide and an immunoglobulin-like domain E(III) that protrudes from the virion surface, followed by a membrane proximal stem and a transmembrane anchor ( Figure 3 ) [45, 112] . The function of E(I) has not been fully characterized, although it has been shown to be involved in the structural rearrangement of the E protein during internalization [112] . The E(II) contains a region known as fusion peptide, which is responsible for the viral fusion activity, and the E domain II also contains serotype-conserved epitopes, and contributes to the E protein dimerization [113, 114] . Previous studies have shown the E(III) is responsible for receptor recognition, which is essential for viral attachment to facilitate viral entry into host cells by receptor-mediated, clathrin-dependent endocytosis (primary method) [73, 102, 103] . Additionally, E(III) also harbours the serotype-specific neutralizing epitopes [115, 116] . Because of the involvement of receptor recognition and attachment, as well as its vital role in mediating viral and cellular membrane fusion to release viral genomic RNA for viral replication, the E glycoprotein is the most important protein facilitating viral entry. Hence, this makes the E protein a good antiviral target to stop viral entry.