Abstract
Flaviviruses including dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), Japanese encephalitis virus (JEV) and tick-borne encephalitis virus (TBEV) are associated with human diseases. Particularly, infected cases of JEV and DENV are reported in south-east Asia. The flaviviruses are covered by envelope proteins, which are the dominant antigen in eliciting neutralizing antibodies and plays an important role in inducing immunologic responses in the infected host. Among three domains of envelope protein, domain III plays the most important role in viral attachment and fusion. Therefore, previous studies have used domain III as a target for drug development. However, there is still no sufficient treatment available. Our works includes two studies. In the first study, we identified a heparin binding motif located on the N-terminal of JEV E protein domain III is responsible for heparin binding. On the other hand, a synthetic peptide with sequence that is corresponding to this region also demonstrates strong affinity to heparin. Our results provide a basis for further understanding the interactions of flaviviruses and GAGs on the host cell surfaces and would be helpful for drug design. In the second study, we used SELEX technology to generate an aptamer which has the ability to target domain III with parallel G-quadruplex structure. Furthermore, we found that residues Q28, H29, G30 and I32 on a completely identical loop among all four DENV strains are involved in the aptamer binding, which leads to the antiviral activity of selected aptamer against all four DENV strains. Our results provide an aptamer as artificial antibody which solves the problem of antibody-dependent enhancement of infection and thus this aptamer may have the potential to be a therapeutic drug.