Targeting sphingolipid metabolism: inhibition of neutral sphingomyelinase 2 impairs coronaviral replication organelle formation.

ABSTRACT: Many plus-strand RNA viruses, including coronaviruses, orchestrate the formation of specialized replication organelles in the cytoplasm of infected cells by specific membrane-associated viral nonstructural proteins (nsp's). This process involves a massive reorganization of intracellular membrane compartments and is thought to depend on a specific set of cellular enzymes that synthesize or modify cellular lipids. Here, we investigated the potential role(s) of specific sphingolipids and related enzymes in coronavirus replication. We observed in cells infected with three different coronaviruses a comparable increase in global ceramide levels, whereas sphingomyelin levels were reduced, suggesting an enhanced conversion of sphingomyelin to ceramide by sphingomyelinases. To test this hypothesis,

SUBMITTER: Salisch F 

PROVIDER: S-EPMC12421859 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature