Host cell plasma membrane lipids (PM lipids)

Host cell plasma membrane lipids are the primary structural components of the cellular envelope, consisting of a complex bilayer of phospholipids, sphingolipids, and sterols like cholesterol [Alberts B, et al., Molecular Biology of the Cell]. These lipids are not merely passive barriers but are active participants in essential cellular processes, including signal transduction, endocytosis, and the maintenance of ion gradients. Specialized microdomains known as lipid rafts concentrate specific lipids and proteins to facilitate efficient communication between the extracellular environment and the cytoplasm [van Meer G, et al., 2008, Nature Reviews Molecular Cell Biology]. In infectious diseases, many enveloped viruses, such as HIV and SARS-CoV-2, exploit these lipid compositions to facilitate attachment, fusion, and entry into the host cell. In oncology, the reorganization of membrane lipids, such as the exposure of phosphatidylserine on the outer leaflet, serves as a marker for cell death and a potential target for immunotherapy [Belzile JP, et al., 2011, Journal of Virology]. Pharmacological agents targeting these lipids often work by disrupting the membrane's physical integrity or by mimicking natural lipids to interfere with metabolic pathways. However, achieving high selectivity for pathogen or diseased cell membranes over healthy host membranes remains a significant therapeutic challenge due to the ubiquitous nature of these molecules.

Other names

Cell membrane lipidsPlasma membrane lipid bilayerMembrane phospholipidsSurface lipidsHost membrane lipids

Drugs targeting host cell plasma membrane lipids act by disrupting the physical integrity of the lipid bilayer, inducing pore formation, altering membrane fluidity, or modulating lipid-dependent signaling pathways such as the Akt/mTOR pathway. Some agents specifically target the externalization of lipids like phosphatidylserine to trigger immune responses or inhibit viral fusion and entry processes [Mollinedo F, et al., 2011, Expert Opinion on Therapeutic Targets; Baginski M, et al., 2003, Biophysical Journal].