In a recent article published in the bioRxiv * prepress server, scientists demonstrated the use of 2-deoxy-D-glucose (2-DG) as a broad-spectrum antiviral agent targeting viruses such as coronavirus 2. severe acute respiratory syndrome (SARS-CoV). -2).
Study: Host-targeted therapy with 2-Deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2. Image credit: Andrii Vodolazhskyi / Shutterstock
Fund
Endemic human coronaviruses (HCoV) and rhinoviruses (RVs) are known causative agents for acute human respiratory tract infections. In healthy individuals, they are usually self-limiting, remaining limited to the upper respiratory tract. However, because viruses circulate seasonally and spread rapidly, they have high annual incidence rates. In addition, these viruses can induce severe morbidity in the elderly, immunocompromised individuals, and children.
CoVs and RVs regulate metabolic processes in host cells, such as glycolysis, to meet their bioenergetic requirements for rapid multiplication. This dependence on CoV and RV, and probably other viruses from human glucose metabolism for replication, makes them an attractive target for the development of potent antiviral therapy. Notably, previous studies have shown that 2-DG, a stable analogue of glucose, inhibits viral multiplication by reversing virus-induced metabolic reprogramming of host cells.
About the study
In the present study, researchers studied the antiviral efficacy of 2-DGs in RVs in the group of minor and major epithelial cell receptors, such as human primary nasal epithelial cells (HNECs). preliminary place of RV multiplication. Simultaneously, the team investigated the influence of glucose on the antiviral efficacy of 2-DG and the intracellular kinetics of 2-DG.
In addition, the scientists evaluated both the positive-stranded ((+) ssRNA) single-stranded ribonucleic acid segments and the template-negative ((-) ssRNA) ssRNA segments to understand in depth the inhibitory impact of 2-DG in the RV replication cycle. The researchers also examined the effect of 2-DG on RV-mediated apoptosis. Finally, they tested the antiviral efficacy of 2-DG against endemic CoVs and the SARS-CoV-2 pandemic strain.
The team determined whether reversing virus-mediated metabolic reprogramming with 2-DG therapy affected viral RNA replication and its ability to cope with respiratory viral infections. Together, the scientists used a host-led method to mitigate CoV and RV infections by using 2-DG in this research.
Results
Collectively, the results of the study showed that treatment with 2-DG reduced the multiplication of all isolates of major and minor RV receptor groups in Henrietta Lacks (HeLa) Ohio cells in standard cultivation conditions and in HNEC. Lower glucose levels improved inhibition of 2-DG-induced RV replication, indicating that 2-DG was more effective under physiological conditions. Based on these findings, 2-DG2-DG could demonstrate even greater antiviral activity through therapeutic target tissues.
2-DG phosphorylated to 2-DG6P in the cell, resulting in intracellular accumulation. After a brief incubation of the cells and 2-DG, 2-DG6P was detected in HNEC and HeLa Ohio cells for several hours.
2-DG significantly decreased both genomic (+) ssRNA and (-) ssRNA template, presumably the source of measurable extracellular viral RNA drop. These data indicate a decrease in viral RNA replication and the amount of virus released due to 2-DG. Accordingly, the assessment of the virus released in HeLa Ohio cells revealed a drop in viral load. In addition, the team found that 2-DG had a protective impact on Ohio HeLa cells by substantially reducing virus-mediated cell death in subsequent analysis.
Treatment of pandemic and endemic CoVs with 2-DG reduced dose-dependent viral load. Compared with RV viral load data, small concentrations of 2-DG were adequate to cause a substantial long-term decrease in viral load in both pandemic and endemic CoVs. The authors mentioned that variations in cell culture patterns could be responsible for the discrepancy between CoV and RV.
Conclusions
According to the study findings, the 2-DG glycolysis inhibitor suppressed RV replication from the major and minor receptor group in a dose-dependent manner. The scientists found that 2-DG inhibited viral RNA synthesis in both negative and positive strands, resulting in fewer descending viruses and a reduction in RV-mediated apoptosis.
2-DG demonstrated a strong antiviral impact on tissue culture under physiological glucose concentrations. However, further research into models similar to physiological environments was required to test this theory. In addition, an analysis of 2-DG intracellular dynamics indicated that the active intermediate, 2-DG6P, was retained for several hours within the cell. The team stated that further research was needed to determine whether 2-DG plays a role in the formation of defective virions among the wrapped viruses.
Overall, current concurrent research into the effect of 2-DG, a glucose analogue, on endemic HCoV and pandemic SARS-CoV-2 showed a significant decrease in viral load. In vitro, 2-DG decreased RV RNA multiplication and reduced RV-mediated apoptosis. In addition, in vitro, 2-DG showed enhanced inhibitory action against RV under physiological glucose levels. 2-DG also reduced the viral load of endemic and pandemic CoV in vitro. These findings indicated that 2-DG could be a broad-spectrum antiviral.
* Important news
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guided by clinical practice / health-related behavior, or treated as established information.
Magazine reference:
- Laxmikant Wali, Michael Karbiener, Scharon Chou, Vitalii Kovtunyk, Adam Adonyi, Irene Goesler, Ximena Contreras, Delyana Stoeva, Dieter Blaas, Johannes Stoeckl, Thomas R Kreil, Guido A Gualdoni, Anna-Dorothea Gorky. (2022). Host-targeted therapy with 2-Deoxy-D-glucose inhibits human rhinoviruses, endemic coronaviruses, and SARS-CoV-2. bioRxiv. two: