Peptides as Therapeutic Agents for Dengue Virus

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

Likewise, Schmidt et al. (2010) also hypothesized and proved that the stem peptides could inhibit dengue virus infection [121] . In the study, a set of overlapping peptides based on the DV2 stem region (from amino acid residues 396-447) were synthesized and tested for their binding affinities with soluble form of DV2 E (sE, covering only the first 395 residues of E) via fluorescence polarization. Among the set of overlapping peptides, a peptide (DV2 419-447 ) was found to bind selectively to the post-fusion of sE with the concentration of half-maximal change in fluorescence polarization (FP IC50) of 0.125 µM and Kd at approximately 150 nM, while the scrambled peptide DV2 419-447 neither bound to pre-fusion nor post-fusion conformers of sE. proposed that the peptide DV2 419-447 inhibited DENV infection through a two-step mechanism during late-stage fusion intermediate, whereby the peptide first binds non-specifically to the viral membrane, followed by specific interaction with the E protein when E proteins undergo conformational rearrangement at low pH. Interestingly, they observed that the reduction of the DV2 419-447 hydrophobicity (by changing the 441-447 amino acid residues) greatly reduced the inhibitory property of the peptide, but not its binding affinity against dengue virus E proteins. This suggested the importance of peptide hydrophobicity to non-specific host membrane interaction before high binding affinity to the DENV E protein.