The antiviral potential of 2-DG was actually its first studied application — predating cancer research by decades. Understanding this mechanism reveals an elegant aspect of 2-DG’s biology.

Viruses that have lipid envelopes — including herpesviruses, coronaviruses, and HIV — rely on host cell glycosylation machinery to synthesise their glycoproteins. These glycoproteins form the surface spikes that viruses use to enter cells. Proper glycosylation is essential for correct glycoprotein folding and function.

2-DG interferes with this process. By blocking glycolysis and depleting the cell’s pool of glucose-derived precursors for glycosylation reactions, 2-DG causes misfolding of viral glycoproteins. The result: impaired viral assembly and reduced infectivity of released virus particles.

Early studies in the 1950s–1970s showed 2-DG reduced replication of herpes simplex virus in cell culture. More recent work has examined 2-DG’s effects on SARS-CoV-2 in cell models. India’s DCGI approved 2-DG as an adjunct therapy for COVID-19 in 2021 based on emergency data — though this decision was controversial and not adopted by other regulatory agencies.

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