Rational Design of Glycolipid‐Based Coacervates for Sequestration of Macromolecules and Enveloped Viruses

Molecular self‐assembly offers a powerful route to engineer sophisticated materials that mimic biological compartmentalization. Inspired by liquid–liquid phase separation (LLPS), which drives the formation of cellular membraneless organelles, we rationally designed glycolipid‐based coacervates by tuning the attractive and repulsive intermolecular interactions. The low‐molecular‐weight glycolipid‐based polyanionic amphiphiles self‐assemble into stable coacervate droplets in an aqueous medium at low micromolar concentrations. The glycolipid‐based self‐coacervates demonstrate the ability to sequester dyes, drug‐like molecules, proteins, and microorganisms, including influenza and lentiviruses. During the sequestration, the coacervates appear to mask the viral surface proteins, blocking viral attachment to host cell receptors and thereby preventing viral entry into host cells.