Membrane insertion of the three main membranotropic sequences from SARS-CoV S2 glycoprotein

In order to complete the fusion process of SARS-CoV virus, several regions of the S2 virus envelope glycoprotein are necessary. Recent studies have identified three membrane-active regions in the S2 domain of SARS-CoV glycoprotein, one situated downstream of the minimum furin cleavage, which is considered the fusion peptide (SARSFP), an internal fusion peptide located immediately upstream of the HR1 region (SARSIFP) and the pre-transmembrane domain (SARSPTM). We have explored the capacity of these selected membrane-interacting regions of the S2 SARS-CoV fusion protein, alone or in equimolar mixtures, to insert into the membrane as well as to perturb the dipole potential of the bilayer. We show that the three peptides interact with lipid membranes depending on lipid composition and experiments using equimolar mixtures of these peptides show that different segments of the protein may act in a synergistic way suggesting that several membrane-active regions could participate in the fusion process of the SARS-CoV.