Metabolomics analysis reveals a potential role SARS-CoV-2 viral proteins in the regulation/perturbation of metabolic pathways associated with altered plasma metabolites in COVID-19 patients

Abstract

Metabolomic analysis of patient`s plasma is a promising approach to the study of molecular mechanisms of viral infections, identification of diagnostic and prognostic biomarkers, and improvement of the current therapies. However, metabolomic analysis is often limited to the identification of overrepresented metabolic processes. Information about the genetic regulation of these processes and the molecular mechanisms and roles of viral proteins in the revealed disturbed function of metabolic processes is overlooked. Metabolomic analysis of plasma of COVID-19 patients and the controls using the high-performance liquid chromatography coupled with tandem mass spectrometric detection (LC-MS/MS) was performed. 103 metabolites were shown to differ significantly in the compared groups. Among KEGG metabolic pathways, amino acid metabolism and the biosynthesis of aminoacyl-tRNAs were overrepresented. Using ANDSystem software, the reconstruction of gene networks describing the potential genetic regulation of metabolic pathways perturbed in COVID-19 patients by SARS-CoV-2 proteins was performed. Viral proteins orf8, E, and nsp5 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 further experimental and computer studies of the regulation of metabolic pathways by SARS-CoV-2 proteins.