ABSTRACT
Rhinoviruses (RVs) and coronaviruses (CoVs) upregulate host cell metabolic pathways such as glycolysis to meet their bioenergetic demands for rapid multiplication. Using the glycolysis inhibitor 2-deoxy-D-glucose (2-DG), we assessed the dose-dependent inhibition of viral replication of minor- and major-receptor group RVs in epithelial cells. 2-DG disrupted RV infection cycle by inhibiting template negative-strand as well as genomic positive-strand RNA synthesis, resulting in less progeny virus and RV-mediated cell death. Assessment of 2-DG’s intracellular kinetics revealed that after a short-exposure to 2-DG, the active intermediate, 2-DG6P, is stored intracellularly for several hours. Finally, we confirmed the antiviral effect of 2-DG on pandemic SARS-CoV-2 and showed for the first time that 2-DG also reduces replication of endemic human coronaviruses (HCoVs). These results provide further evidence that 2-DG could be utilized as a broad-spectrum antiviral.
HIGHLIGHTS
2-DG inhibits replication of minor- and major-group rhinoviruses in epithelial cells including human nasal epithelial cell.
2-DG disrupts rhinovirus infection cycle and reduces rhinovirus-mediated cell death in vitro.
2-DG treatment attenuates viral load of endemic coronaviruses 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.
Footnotes
Minor changes in text and reorganisation of figures.