Peptides as Therapeutic Agents for Dengue Virus

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

The DENV E structural proteins have been well determined using nuclear magnetic resonance spectroscopy, X-ray crystallography and cryo-electron microscopy [112, 117, 118] . Recent advancements in the understanding of the high-resolution E structure have allowed researchers to utilize the information in combination with in silico molecular drug designing methods to search for potential antiviral candidates. Several research groups have utilized different strategies including in silico drug design to screen for novel antiviral peptides against the E protein (Table 1) . By using Wimley-White interfacial hydrophobicity scale (WWIHS) in combination with known structural data of the E protein, Hrobowski et al. (2005) were the first group to identify a novel peptide DN59, corresponding to the stem region of E, which showed >99% DENV-2 inhibition at <25 µM [119] . The D59 peptide was suggested to function through a sequence of specific mechanisms as a scrambled peptide failed to inhibit DENV infection. It was hypothesized that the DN59 peptide might interfere with the intramolecular interaction, disrupt structural rearrangements of fusion proteins or interact with target cell surface components to exert its inhibitory effects [119] . The mechanism of action for peptide DN59 was further evaluated by a later study (2012) where it was shown that the peptide D59 inhibited DENV infectivity by interacting directly with virus particles, causing the formation of holes at the five-fold vertices in the virus particles [120] . This led to the release of viral genomic RNA and exposure of the viral RNA to exogenous RNase [120] .