Comparing the Mode of Action of Two Membrane-Targeting Antiviral Peptides: A Neutron Reflectometry Study

There is significant interest in developing broad-spectrum antiviral peptides that inhibit membrane-enveloped viruses and to elucidate design principles that can aid antiviral peptide engineering to further improve potency and selectivity for eventual clinical translation. Within this scope, the AH and C5A peptides are two widely studied antiviral peptides, however, the atomistic details of how these two peptides distinctly interact with lipid membranes remains unknown. Addressing this gap is critical from a human health and safety perspective because the AH peptide selectively targets highly curved membranes such as those of virus particles and leaves human cell membranes unperturbed whereas the C5A peptide indiscriminately solubilizes high- and low-curvature membranes. In this project, we seek to employ neutron reflectometry to characterize how the AH and C5A peptides interact with supported lipid bilayer (SLB) platforms across several bulk peptide concentrations in order to determine the mode of action of each peptide. Our team is composed of expert researchers in the fields of antiviral peptides, model membranes, and neutron reflectometry, and we anticipate that the resulting insights from this project will provide unprecedented knowledge about the structure and function of membrane-targeting antiviral peptides, especially in combination with data from other ongoing experimental, modeling, and simulation efforts.