Glycolytic inhibitor 2-deoxy-d-glucose attenuates SARS-CoV-2 multiplication in host cells and weakens the infective potential of progeny virions

Virus-infected host cells switch their metabolism to a more glycolytic phenotype, required for new virion synthesis and packaging. Therefore, we investigated the effect and mechanistic action of glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) on virus multiplication in host cells following SARS-CoV-2...

Full description

Saved in:
Bibliographic Details
Published in:Life sciences (1973) 2022-04, Vol.295, p.120411-120411, Article 120411
Main Authors: Bhatt, Anant Narayan, Kumar, Abhishek, Rai, Yogesh, Kumari, Neeraj, Vedagiri, Dhiviya, Harshan, Krishnan H., Chinnadurai, Vijayakumar, Chandna, Sudhir
Format: Article
Language:English
Subjects:
2-DG
Adenosine Triphosphate - metabolism
Animals
Antiviral Agents - pharmacology
Cell Proliferation - drug effects
Cell Survival - drug effects
Chlorocebus aethiops
COVID-19
COVID-19 - metabolism
COVID-19 - virology
COVID-19 Drug Treatment
Deoxyglucose - pharmacology
Glucose - metabolism
Glycolysis
Glycolysis - drug effects
Glycosylation
Host-Pathogen Interactions - drug effects
Mannose - pharmacology
SARS-CoV-2
SARS-CoV-2 - drug effects
SARS-CoV-2 - pathogenicity
SARS-CoV-2 - physiology
Spike Glycoprotein, Coronavirus - metabolism
Unglycosylation
Vero Cells
Virion - drug effects
Virion - pathogenicity
Virus Replication - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Virus-infected host cells switch their metabolism to a more glycolytic phenotype, required for new virion synthesis and packaging. Therefore, we investigated the effect and mechanistic action of glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) on virus multiplication in host cells following SARS-CoV-2 infection. SARS-CoV-2 induced change in glycolysis was examined in Vero E6 cells. Effect of 2-DG on virus multiplication was evaluated by RT-PCR (N and RdRp genes) analysis, protein expression analysis of Nucleocapsid (N) and Spike (S) proteins and visual indication of cytopathy effect (CPE), The mass spectrometry analysis was performed to examine the 2-DG induced change in glycosylation status of receptor binding domain (RBD) in SARS-CoV-2 spike protein. We observed SARS-COV-2 infection induced increased glucose influx and glycolysis, resulting in selectively high accumulation of the fluorescent glucose analog, 2-NBDG in Vero E6 cells. 2-DG inhibited glycolysis, reduced virus multiplication and alleviated cells from virus-induced cytopathic effect (CPE) in SARS-CoV-2 infected cells. The progeny virions produced from 2-DG treated cells were found unglycosylated at crucial N-glycosites (N331 and N343) of the receptor-binding domain (RBD) in the spike protein, resulting in production of defective progeny virions with compromised infective potential. The mechanistic study revealed that the inhibition of SARS-COV-2 multiplication is attributed to 2-DG induced glycolysis inhibition and possibly un-glycosylation of the spike protein, also. Therefore, based on its previous human trials in different types of Cancer and Herpes patients, it could be a potential molecule to study in COVID-19 patients. [Display omitted] •SARS-CoV-2 infection induces glucose influx and glycolysis in Vero E6 cells.•2-DG mediated glycolytic inhibition can attenuate SARS-COV-2 multiplication.•Progeny virions from 2-DG treated cells have reduced infective potential possibly due to unglycosylation of spike protein.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2022.120411