2-deoxy-D-glucose is a synthetic glucose analog and a potent inhibitor of glycolysis. Preclinical models demonstrated antiviral effects of 2-deoxy-D-glucose by inducing a glucose-deprived state in cells, which interferes with viral replication.

This was a phase I, first-in-human, double-blind, randomized, placebo-controlled, dose-escalation trial of single (cohort 1: 100µl in one nostril, cohort 2: 200µl in one nostril, cohort 3: 200µl in both nostrils) and multiple (cohort 4: four-times 200µl/day in one nostril, cohort 5: four-times 200µl/day in both nostrils, cohort 6: six-times 200µl/day in both nostrils; all for seven days) ascending doses of intranasal 3.5% 2-deoxy-D-glucose in normal healthy volunteers with the primary objective of investigating safety and tolerability. Drug concentrations were measured in plasma and in nasal wash fluid.

Forty-five healthy volunteers participated in this study. Single and multiple doses of 2-deoxy-D-glucose were well-tolerated, with no safety signals or treatment-related serious or severe adverse events observed throughout the trial. Pharmacokinetics showed virtually absent systemic absorption of intranasal 2-deoxy-D-glucose, while intranasal maximum drug concentrations were comparable to those shown to have antiviral effects in vitro.

Intranasal 2-deoxy-D-glucose, a novel intranasal therapeutic treatment for acute viral infections was safe and well-tolerated in healthy volunteers. These data support the further clinical development of 2-deoxy-D-glucose for treating viral infections in the target population (NCT05314933).