Interaction of a peptide from the pre-transmembrane domain of the severe acute respiratory syndrome coronavirus spike protein with phospholipid membranes

The severe acute respiratory syndrome coronavirus (SARS-CoV) envelope spike (S) glycoprotein, a Class I viral fusion protein, is responsible for the fusion between the membranes of the virus and the target cell. In order to gain new insight into the protein membrane alteration leading to the viral fusion mechanism, a peptide pertaining to the putative pre-transmembrane domain (PTM) of the S glycoprotein has been studied by infrared and fluorescence spectroscopies regarding its structure, its ability to induce membrane leakage, aggregation, and fusion, as well as its affinity toward specific phospholipids. We demonstrate that the SARS-CoV PTM peptide binds to and interacts with phospholipid model membranes, and, at the same time, it adopts different conformations when bound to membranes of different compositions. As it has been already suggested for other viral fusion proteins such as HIV gp41, the region of the SARS-CoV protein where the PTM peptide resides could be involved in the merging of the viral and target cell membranes working synergistically with other membrane-active regions of the SARS-CoV S glycoprotein to heighten the fusion process and therefore might be essential for the assistance and enhancement of the viral and cell fusion process.     

Structural and dynamic characterization of the interaction of the putative fusion peptide of the S2 SARS-CoV virus protein with lipid membranes

The SARS coronavirus (SARS-CoV) envelope spike (S) glycoprotein, a Class I viral fusion protein, is responsible for the fusion between the membranes of the virus and the target cell. In the present work, we report a study of the binding and interaction with model membranes of a peptide pertaining to the putative fusion domain of SARS-CoV, SARS FP, as well as the structural changes that take place in both the phospholipid and the peptide molecules upon this interaction. From fluorescence and infrared spectroscopies, the peptide ability to induce membrane leakage, aggregation and fusion, as well as its affinity toward specific phospholipids, was assessed. We demonstrate that SARS FP strongly partitions into phospholipid membranes, more specifically with those containing negatively charged phospholipids, increasing the water penetration depth and displaying membrane-activity modulated by the lipid composition of the membrane. Interestingly, peptide organization is different depending if SARS FP is in water or bound to the membrane. These data suggest that SARS FP could be involved in the merging of the viral and target cell membranes by perturbing the membrane outer leaflet phospholipids and specifically interacting with negatively charged phospholipids located in the inner leaflet.