Peptides as Therapeutic Agents for Dengue Virus

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

Viral proteases have been shown to serve as good inhibitory targets. For instance, protease inhibition was shown to be a successful strategy in treating HIV infection [151] . The HIV-1 protease cleaves the translated polypeptide chain into smaller functional proteins, thereby allowing the virus particle to mature [152] . By inhibiting the protease, the immature virus particles would not be able to transform into the mature virion, hence obstructing the viral replication. Several HIV-1 protease inhibitors were discovered and used clinically, such as saquinavir, ritonavir, indinavir, nelfinavir, amprenavir (and its prodrug, fosamprenavir), lopinavir, atazanavir, and darunavir [153] . Similarly, the NS5, NS3 and NS2B (co-factor) proteins were known to play major roles in enzymatic activities for DENV infection, thus making them ideal antiviral targets [154, 155] . After DENV infection, translation of the viral genome will give rise to a polyprotein containing three structural and seven non-structural proteins. The polyprotein will be cleaved into individual proteins during virus maturation by the host proteases (signalase and furin) on the luminal side of the endoplasmic reticulum, as well as by the viral serine protease (NS2B-NS3 protease) on the cytoplasmic side to ensure the success of viral replication and maturation [49, 154, 156] . DENV NS3 contains a trypsin-like protease and it requires the NS2B cofactor to be active to cleave the DENV polyprotein at the Ser-His-Asp catalytic triad [157] [158] [159] [160] .