Cholesterol: A key player in membrane fusion that modulates the efficacy of fusion inhibitor peptides.

The interaction of cholesterol with the neighboring lipids modulates several physical properties of the membrane. Mostly, it affects membrane fluidity, membrane permeability, lateral diffusion of lipids, bilayer thickness, and water penetration into the lipid bilayer. Due to the smaller head group to hydrophobic cross-sectional area of the tail, cholesterol induces intrinsic negative curvature to the membrane. The interaction of cholesterol with sphingolipids forms lipid rafts; generates phase separation in the membrane. The cholesterol-dependent modifications of membrane physical properties modulate viral infections by affecting the fusion between viral and host cell membranes. Cholesterol demonstrates a strong impact on the structure, depth of penetration, conformation, and organization of fusion peptides in membrane milieu. Further, cholesterol has been implicated to modify the fusion inhibitory efficiency of peptide-based membrane fusion inhibitors.