Metabolic reprogramming as a novel therapeutic target for Coxsackievirus B3

ABSTRACT

Coxsackievirus B3 (CVB3) is a single-stranded RNA virus that belongs to the Enterovirus genus. CVB3 is a human pathogen associated with serious conditions such as myocarditis, dilated cardiomyopathy, and pancreatitis. However, there are no therapeutic interventions to treat CVB3 infections. In this study, we found that CVB3 induced metabolic alteration in host cells through increasing glycolysis level, as indicated by an increase in the extracellular acidification rate (ECAR). CVB3-mediated metabolic alteration was confirmed by metabolite change analysis using gas chromatography-mass spectrometry (GC-MS). Based on findings, a strategy to inhibit glycolysis has been proposed to treat CVB3 infection. Indeed, glycolysis inhibitors (2-Deoxy-D-glucose, sodium oxide) significantly reduced CVB3 titers after CVB3 infection, indicating that glycolysis inhibitors can be used as effective antiviral agents. Taken together, our results reveal a novel mechanism by which CVB3 infection is controlled by regulation of host cell metabolism.

KEYWORDS:

• Coxsackievirus B3
• metabolic alteration
• glycolysis inhibitors
• antiviral effect

Acknowledgments

MUK, HWK, YB and JTP conceived of and designed the experiments. MUK, YJG, YJK, JYP, ESS, HL, YHL and GK performed the experiments. JKK and JYY analyzed the data. MUK, HWK, YB and JTP wrote and edited the paper.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This research was supported by an Incheon National University research [grant number 2019-0406]. This research was also supported by the Technology Innovation Program (Alchemist Project, 20019181) through the Korea Evaluation Institute of Industrial Technology (KEIT) funded by the Ministry of Trade, Industry and Energy.