Targeting Acid Sphingomyelinase: New Frontiers in Antiviral Drug Development

The field of viral pathogenesis research is rapidly uncovering the importance of host-cell lipid metabolism as a key determinant of viral replication and infection. Among lipid-modifying enzymes, acid sphingomyelinase (ASM) has emerged as a pivotal factor in the regulation of cell membrane dynamics, endocytic trafficking, and inflammatory response—processes frequently hijacked by viruses. Recent evidence suggests that ASM activity modulates the entry, replication, and immune evasion mechanisms of numerous viruses, including SARS-CoV-2, influenza, and Ebola virus. Despite the growing understanding of ASM’s biological significance, its therapeutic potential in antiviral drug development remains underexplored, representing a significant gap in translational virology. Studies using functional inhibitors of ASM (FIASMAs) have shown promise in reducing viral load and mitigating virus-induced cellular damage, yet the mechanistic bases and clinical applicability of these findings require broader investigation.This Research Topic aims to explore how modulation of acid sphingomyelinase and sphingolipid metabolism can offer novel antiviral strategies. By integrating insights from molecular virology, pharmacology, and host-pathogen interaction studies, the Topic seeks to clarify the multifunctional roles of ASM in viral infection cycles and identify opportunities to leverage this enzyme as a druggable target. Key objectives include understanding the interplay between ASM activity and viral pathogenesis, assessing the antiviral potential of existing and novel ASM inhibitors, and defining biomarkers associated with sphingomyelin metabolism in infection outcomes. Collectively, the Topic aims to foster translational pathways that bridge fundamental discoveries with therapeutic innovation.To gather further insights into the mechanisms and translational applications of ASM modulation in viral infections, we welcome articles addressing, but not limited to, the following themes:o Molecular mechanisms linking ASM activation to viral entry and replicationo Role of sphingomyelin and ceramide signaling in host immune responses to viruseso Sphingolipids, sphingolipid-binding proteins, and sphingolipid-modifying enzymes at the host-virus interface.o Pharmacological profiling and repurposing of FIASMAs for antiviral therapieso Structural and computational studies identifying druggable sites of ASMo ASM-mediated pathways contributing to viral persistence or pathogenicityo Biomarker discovery and lipidomic approaches in virus-infected cellso Preclinical and clinical studies assessing ASM modulation in antiviral treatmento Crosstalk between ASM activity and other host lipid-regulating enzymesArticle types: Original Research, Review, Mini Review, Hypothesis and Theory, Perspective, and Brief Research Report. Topic editors: Sreekanth Gopinathan Pillai, Jeffrey B Travers, Craig Rohan Source: https://www.frontiersin.org/research-topics/83375/targeting-acid-sphingomyelinase-new-frontiers-in-antiviral-drug-development