Peptides as Therapeutic Agents for Dengue Virus

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

The prM protein (about 21 kDa) is the precursor of the M protein (approximately 8 kDa). The cleavage of the prM protein by the cellular protease (furin) would separate the prM protein into the "pr" peptide (1-91 residues), the ectodomain (92-130 residues) and the M protein (131-166 residues) [45, 142, 143] . The hydrophilic N-terminal region of the protein is responsible for coding the glycosylated "pr" segment of the prM protein. The prM is believed to protect the E protein from conformational changes during the maturation pathway in the acidic environment of the trans-golgi network. A previous study has shown that prM-containing-virus is more resistant to the low pH environment [144] . Upon release of the matured virions, "pr" will be separated, leaving the E and M proteins on the surface of the mature DENV. In a recent study, a peptide inhibitor (MLH40) mimicking the conserved ectodomain of the M protein was designed and it was shown to inhibit all four DENV serotypes with an IC50 of 24-31 µM [145] . Docking results indicated that MLH40 bound to the interior site of E homodimer, which is the same interacting site for the native M protein against the E protein.