ABSTRACT
Rhinoviruses (RVs) and coronaviruses (CoVs) upregulate host cell metabolic pathways including glycolysis to meet their bioenergetic demands for rapid multiplication. Using the glycolysis inhibitor 2-deoxy-D-glucose (2-DG), we confirm the dose-dependent inhibition of minor- and major-receptor group RV replication. We demonstrate that 2-DG suppresses viral positive-as well as negative-strand RNA synthesis, resulting in lower amounts of progeny virus and RV-mediated cell death. In tissue culture with physiologic glucose levels, 2-DG has a pronounced antiviral effect. Further, assessment of 2-DG’s intracellular kinetics revealed that the active intermediate, 2-DG6P, is stored intracellularly for several hours. Our concurrent study of 2-DG’s impact on pandemic SARS-CoV-2 and endemic HCoVs demonstrated a significant reduction in viral load. Collectively, these results suggest 2-DG to be a broad-spectrum antiviral.
HIGHLIGHTS
2-DG, a glucose analogue, inhibits RV RNA replication and reduces RV-mediated cell death in vitro.
2-DG exhibits increased inhibitory activity against RV in physiological glucose concentrations in vitro.
2-DG attenuates viral load of pandemic and endemic CoVs in vitro.
Competing Interest Statement
L.W., S.C., V.K., A.A., X.C., D.S., A.-D.G., J.S. and G.G. are/were employees and/or shareholders of G.ST Antivirals, Vienna, Austria. G.G. and J.S. are co-inventors of patent application related to parts of the manuscript. M.K. and T.R.K. are employees and stockholders of Takeda Manufacturing Austria AG, Vienna, Austria.
