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Glycolytic inhibitor 2-deoxy-d-glucose attenuates SARS-CoV-2 multiplication in host cells and weakens the infective potential of progeny virions.
Bhatt, Anant Narayan; Kumar, Abhishek; Rai, Yogesh; Kumari, Neeraj; Vedagiri, Dhiviya; Harshan, Krishnan H; Chinnadurai, Vijayakumar; Chandna, Sudhir.
  • Bhatt AN; Institute of Nuclear Medicine & Allied Sciences, Delhi, India. Electronic address: anant.inmas@gov.in.
  • Kumar A; Institute of Nuclear Medicine & Allied Sciences, Delhi, India.
  • Rai Y; Institute of Nuclear Medicine & Allied Sciences, Delhi, India.
  • Kumari N; Institute of Nuclear Medicine & Allied Sciences, Delhi, India.
  • Vedagiri D; CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500007, India; Academy for Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • Harshan KH; CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500007, India; Academy for Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • Chinnadurai V; Institute of Nuclear Medicine & Allied Sciences, Delhi, India.
  • Chandna S; Institute of Nuclear Medicine & Allied Sciences, Delhi, India.
Life Sci ; 295: 120411, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1683412
ABSTRACT

AIMS:

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. MAIN

METHODS:

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. KEY

FINDINGS:

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.

SIGNIFICANCE:

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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Deoxyglucose / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study Limits: Animals Language: English Journal: Life Sci Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Deoxyglucose / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Experimental Studies / Prognostic study Limits: Animals Language: English Journal: Life Sci Year: 2022 Document Type: Article