The roles of sugar metabolism mechanisms and metabolites in viral infections

Viral infections pose a persistent challenge to global health by triggering sophisticated molecular interactions and extensive metabolic reprogramming within host organisms. Glycolysis-a central energy metabolism pathway-is dynamically and bidirectionally regulated during infection, reflecting a continuous metabolic interplay between pathogen and host. Rather than maintaining a static metabolic state, glycolytic flux is shaped by competing demands: viruses actively stimulate glycolysis to support replication, while hosts suppress it as a defensive strategy. This regulatory balance shifts across distinct stages of infection-from viral entry and replication peaks to immune clearance-resulting in phase-specific fluctuations in glycolytic activity that reveal a dynamic metabolic tug-of-war. In this review, we synthesize current understanding of how viruses recurrently activate host glycolysis to enhance replication, detailing conserved mechanisms of metabolic hijacking and the multilayered counterstrategies employed by the host. We further evaluate emerging therapeutic approaches, including targeted glycolytic inhibitors and combined immunomodulatory regimens, while addressing challenges related to specificity and efficacy. Finally, we highlight promising research directions such as tissuespecific nanodelivery platforms and single-cell multi-omics integration, which together offer a conceptual framework for developing next-generation antiviral therapies.

Journal

VIROLOGY

Year

2026

Volume

615

ISSN

0042-6822

eISSN

1089-862X

DOI

10.1016/j.virol.2025.110764

WoS UID

WOS:001632844600001