The membrane-active regions of the dengue virus proteins C and E.

We have identified the membranotropic regions of proteins C and E of DENV virus by performing an exhaustive study of membrane rupture induced by two C and E-derived peptide libraries on model membranes having different phospholipid compositions as well as its ability to modulate the DEPE L(β)-L(α) and L(α)-H(II) phospholipid phase transitions. Protein C presents one hydrophobic leakage-prone region coincidental with a proposed membrane interacting domain, whereas protein E presents five membrane-rupture zones coincidental with different significant zones of the protein, i.e., the fusion peptide, a proline-rich sequence, a sequence containing a hydrophobic pocket as well as the stem and transmembrane domains of the protein. The identification of these membrane-active segments supports their role in viral membrane fusion, formation of the replication complex and morphogenesis and therefore attractive targets for development of new anti-viral compounds.