Glycolytic stress deteriorates 229E virulence to improve host defense response

Area of Science:

• Virology
• Cellular Metabolism
• Drug Discovery

Background:

• Viral infections pose treatment challenges due to viral adaptability and host cell metabolic alterations.
• Coronaviruses uniquely stimulate glycolysis, impair mitochondrial function, and compromise host cells.

Purpose of the Study:

• To investigate the efficacy of 2-Deoxy-d-glucose (2-DG) in inhibiting coronavirus-induced metabolic changes.
• To evaluate 2-DG's impact on antiviral host defense systems during coronavirus infection.

Main Methods:

• Utilized fluorescent 2-NBDG, a glucose analog, to monitor glucose uptake in infected cells.
• Administered 2-DG to coronavirus-infected host cells to assess its effects on viral replication and cell viability.
• Investigated the role of high-affinity glucose transporters in 2-DG uptake.

Main Results:

• 229E human coronavirus significantly increased glycolysis, evidenced by elevated 2-NBDG concentrations in infected cells.
• 2-DG treatment reduced viral replication, suppressed infection-induced cell death, and mitigated cytopathic effects.
• Low doses of 2-DG inhibited glucose uptake, mediated by amplified high-affinity glucose transporters in infected cells.

Conclusions:

• 2-DG demonstrates potential as an antiviral agent against coronaviruses by modulating host cell metabolism.
• Targeting glucose metabolism with 2-DG can enhance the host defense system in coronavirus-infected cells.
• Further research into 2-DG as a therapeutic strategy for viral infections is warranted.