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. 2021 Jun 21;12:3818. doi: 10.1038/s41467-021-24007-w

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, b Analysis and regulation of significantly altered pathways of mock- and SARS-CoV-2-infected (24 h p.i., MOI = 0.1) VeroFM cells (a) or Calu-3 cells (b). The y-axis shows the (median) log2 fold change (FC) of all significantly altered metabolites of the indicated pathway while the –log10 corrected p-value (false discovery rate (FDR)) is shown on the x-axis. The size of the circles illustrates the number of significantly changed metabolites in relation to all metabolites of a specific pathway. c Analysis of the autophagic pathway and the involved metabolites: ‘amino acids’ and ‘GSH metabolism’ (orange), ‘nucleotides’ (blue), ‘glycolysis’ (green), ‘polyamine metabolism’ (red) and ‘O-GalNAcylation’ (purple) in mock- and SARS-CoV-2-infected (24 h p.i.) VeroFM and Calu-3 cells. For a–c Error bars represent SEM. n = 4 biological samples per group of one experiment. All p-values were determined by a two-way ANOVA and Tukey´s post hoc test. FDRs were adjusted using the Benjamini-Hochberg method. Abbreviations: 1,3-BPG, 1,3-bisphosphoglyceric acid; 3-PGA, 3-phosphoglyceric acid; ADP, adenosine diphosphate; AKT1, RAC-alpha serine/threonine-protein kinase; ala, alanine; AMP, adenosine monophosphate; AMPK, AMP-activated protein kinase; arg, arginine; asn, asparagine; asp, asparagine; ATP, adenosine triphosphate; aut, autophagosome; BECN1, beclin-1; bio., biosynthesis; CTP, cytidine triphosphate; CoA, coenzyme A; cys, cysteine; cysgly, cysteinylglycine; cyst, cystathionine; dCTP, deoxycytidine triphosphate; dicarbox., dicarboxylate; elF5AH, eukaryotic translation initiation factor 5A hypusinated; EP300, histone acetyltransferase p300; F1P, fructose 1-phosphate; F6P, fructose 6-phosphate; F-1,6-BP, fructose 1,6-bisphosphate; FKBP51, 51 kDa FK506-binding protein; G6-P, glucose 6-phosphate; gln, glutamine; glu, glutamic acid; gly, glycine; glyox, glyoxylate; GSH, glutathione (reduced); GTP, guanosine triphosphate; hcys, homocysteine; his, histidine; ile, isoleucine; lac, lactic acid; leu, leucine; lys, lysine; mal, malic acid; met, methionine; met., metabolism; modific., modification; mTORC1, mechanistic target of rapamycin complex 1; NAcput, N-acetylputrescine; NAcspd, N-acetylspermidine; orn, ornithine; PEP, phosphoenolpyruvic acid; phe, phenylalanine; PHLPP, PH domain leucine-rich repeat-containing protein phosphatase; PPP, pentose phosphate pathway; pro, proline; prot., protein; put, putrescine; pyr, pyruvic acid; resid., residue; ROS, reactive oxygen species; S7P, sedoheptulose-7-phosphate; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; SAT1, diamine acetyltransferase 1; SKP2, S-phase kinase-associated protein 2; ser, serine; spd, spermidine; spm, spermine; tau, taurine; TFEB, transcription factor EB; thr, threonine; trp, tryptophan; tyr, tyrosine; UDP-GalNAc, UDP-N-acetylgalactosamine; UDP, uridine diphosphate; UTP, uridine triphosphate; val, valine.