Metabolic reprogramming as a novel therapeutic target for Coxsackievirus B3

代谢重编程作为柯萨奇病毒 B3 的新治疗靶点

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作者:Myeong Uk Kuk, Yun Ji Ga, Ye Jin Kim, Ji Yun Park, Eun Seon Song, Haneur Lee, Yun Haeng Lee, Gahyun Ko, Jae Kwang Kim, Jung-Yong Yeh, Hyung Wook Kwon, Youngjoo Byun, Joon Tae Park

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.

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