Computational Insights into the Antiviral Properties of the Antimicrobial Peptide β-Amyloid.

Beta-amyloid (Aβ) is a peptide that forms extracellular plaques in the brain of patients affected by Alzheimer's disease. Numerous studies have been conducted on Aβ's characteristics, revealing its antibacterial and antiviral properties. Indeed, Aβ can bind to molecules attached to the surface of cell membranes, such as GM1 ganglioside, which are also known as points of entry for viruses. This binding could then explain its antiviral properties, as it may prevent the binding of proteins found on the surface of viruses. All-atom molecular dynamics simulations on protein-membrane systems were conducted to investigate this process. The selected proteins were Aβ42, Aβ40, VP1 from simian virus 40, VP8* from rotavirus, and HSV-1gD (herpes simplex virus 1). These last three viral proteins are already known to interact with either GM1 or Aβ. The membrane was a bilayer containing five different lipids (phospholipids, cholesterol, and GM1). Protein-membrane interactions were studied through the formation of hydrogen bonds and salt bridges over time, and the quantification of the interaction energies. Favorable interactions were observed between all studied proteins and GM1 lipids, especially for VP8*, where a strong network of interactions with the arginine residues was identified. Moreover, we demonstrate that a larger protein does not necessarily result in higher interaction energies, suggesting that smaller peptides may compete with these larger proteins.