Peptides as Therapeutic Agents for Dengue Virus

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

Additionally, multiple strategies could also be incorporated into peptide drug development to enhance the antiviral properties of peptides. These include the mutagenesis assays to identify the vital amino acids which are responsible for the inhibitory effects and the addition of cell penetrating peptides to increase the cell permeability of peptides. For example, the IC50 of two antiviral peptides (DN57 opt and DN81 opt) were successfully reduced to 8 μM and 40 μM, respectively, after amino acid optimization was performed via residue-specific all-atom probability discriminatory function approach [119, 138] . Similarly, Schmidt and co-workers (2010a, 2010b) successfully enhanced the antiviral properties of the identified peptides after optimizations via mutagenesis assays and the addition of a solubility tag [121, 136] . On the other hand, due to the hydrophilicity and conformation properties of peptides, cellular uptake of peptides is constrained [189, 190] . Oral bioavailability of peptides is therefore limited by the membrane barrier. To overcome this challenge, cell-penetrating peptides (CPP) can be incorporated into the peptide sequence to act as a cargo delivery in carrying antiviral peptide across the permeability barrier and entering cells to exert its inhibitory activity [191] . For instance, by conjugating the tat peptide (derived from the HIV-1 transcriptional activator protein) to galactosidase protein, it enabled the delivery of the fusion protein to all the tissues in mice while those without tat peptide-conjugated were restrained [192] . With the advancement of technology, the drawbacks of peptides serving as antiviral agents can therefore be overcome by various strategies. This, in turn, will aid the development and use of peptides as therapeutics.