Plasma metabolomics and gene regulatory networks analysis reveal the role of nonstructural SARS-CoV-2 viral proteins in metabolic dysregulation in COVID-19 patients

V. A. Ivanisenko, E. V. Gaisler, N. V. Basov, A. D. Rogachev, S. V. Cheresiz, T. V. Ivanisenko, P. S. Demenkov, E. L. Mishchenko, O. P. Khripko, Yu I. Khripko, S. M. Voevoda, T. N. Karpenko, A. J. Velichko, M. I. Voevoda, N. A. Kolchanov, A. G. Pokrovsky

Research output: Contribution to journalArticlepeer-review

Abstract

Metabolomic analysis of blood plasma samples from COVID-19 patients is a promising approach allowing for the evaluation of disease progression. We performed the metabolomic analysis of plasma samples of 30 COVID-19 patients and the 19 controls using the high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometric detection (LC–MS/MS). In our analysis, we identified 103 metabolites enriched in KEGG metabolic pathways such as amino acid metabolism and the biosynthesis of aminoacyl-tRNAs, which differed significantly between the COVID-19 patients and the controls. Using ANDSystem software, we performed the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins. The nonstructural proteins of SARS-CoV-2 (orf8 and nsp5) and structural protein E were involved in the greater number of regulatory pathways. The reconstructed gene networks suggest the hypotheses on the molecular mechanisms of virus-host interactions in COVID-19 pathology and provide a basis for the further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins. Our metabolomic analysis suggests the need for nonstructural protein-based vaccines and the control strategy to reduce the disease progression of COVID-19.

Original languageEnglish
Article number19977
Number of pages12
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2022

Keywords

  • Humans
  • SARS-CoV-2/genetics
  • COVID-19
  • Gene Regulatory Networks
  • Chromatography, Liquid
  • Tandem Mass Spectrometry
  • Plasma
  • Viral Proteins/genetics
  • Disease Progression

OECD FOS+WOS

  • 1.06 BIOLOGICAL SCIENCES

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