Behind the membranous curtain—lipid dynamics and functions in coronaviral replication

ABSTRACT Lipids are naturally occurring hydrophobic biomolecules characterized by remarkable structural diversity. This includes various types of head groups, varying fatty acid chain lengths, degrees of unsaturation, and stereochemical configurations. Such variability enables lipids to serve multiple biological functions, such as forming membranes, storing energy, and facilitating signaling. Given their diverse roles, it is not surprising that approximately 5% of genes in eukaryotic cells are involved in lipid biosynthesis pathways. The multifunctional nature of lipids also makes them attractive targets for pathogens, including viruses, as cellular lipids are involved in and manipulated throughout every stage of viral replication. In the initial phase of replication, viruses exploit existing cellular lipids for entry and trafficking. After the replication is established and viral proteins are processed, extensive reprogramming of lipid synthesis and redistribution supports viral replication, assembly, and other processes. This review focuses on how coronaviruses, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), utilize different lipid species and related cellular enzymes to interfere with lipid dynamics and functions and how this affects the different stages of coronaviral replication in vitro . Besides illuminating virus-host lipid interactions, this review identifies remaining open questions and promising new avenues for future mechanistic research.