Peptides as Therapeutic Agents for Dengue Virus

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

In another study, 15 peptide inhibitors against the NS2B-NS3 protease were modified via molecular modelling method [170] . Results from the ADME/Tox calculation indicated that the peptide inhibitor 11 (Bz-Nle-Lys-Arg-Bip) possessed the best pharmacokinetic properties among all inhibitors due to its ability to be better absorbed into the intestine and to remain inactive in the central nervous system [170] . This results supported the use of Bz-Nle-Lys-Arg as the lead candidate for drug development against DENV by targeting the NS2B-NS3 protease. On the other hand, several hexapeptides derived from the NS2B-NS3 protease cleavage sites were synthesized and they were shown to inhibit DENV in a low micromolar range [171] . Among all candidates, the best hexapeptide inhibitor was derived from the NS2A/NS2B region with a Ki value of 12 µM. Likewise, several peptidic α-keto amide inhibitors mimicking the NS3/NS4 region were designed and two of the peptidic inhibitors were found to inhibit the NS3 protease with Ki values of 16 and 47 µM, respectively [172] .