Intracellular peptides in SARS-CoV-2-infected patients.

Luiz Felipe Martucci, Rosangela A S Eichler, Renée N O Silva, Tiago J Costa, Rita C Tostes, Geraldo F Busatto, Marilia C L Seelaender, Alberto J S Duarte, Heraldo P Souza, Emer S Ferro
Author Information
  1. Luiz Felipe Martucci: Department of Pharmacology, Biomedical Sciences Institute, São Paulo 05508-000, Brazil.
  2. Rosangela A S Eichler: Department of Pharmacology, Biomedical Sciences Institute, São Paulo 05508-000, Brazil.
  3. Renée N O Silva: Department of Pharmacology, Biomedical Sciences Institute, São Paulo 05508-000, Brazil.
  4. Tiago J Costa: Department of Pharmacology, Ribeirao Preto Medical School, Ribeirão Preto 14049-900, Brazil.
  5. Rita C Tostes: Department of Pharmacology, Ribeirao Preto Medical School, Ribeirão Preto 14049-900, Brazil.
  6. Geraldo F Busatto: Department of Psichiatry, Medical School and Hospital das Clínicas, University of São Paulo, 01246-903 SP, Brazil.
  7. Marilia C L Seelaender: Department of Surgery, Medical School and Hospital das Clínicas, University of São Paulo, 01246-903 SP, Brazil.
  8. Alberto J S Duarte: Department of Patology, Medical School and Hospital das Clínicas, University of São Paulo, 01246-903 SP, Brazil.
  9. Heraldo P Souza: Department of Internal Medicine, Medical School and Hospital das Clínicas, University of São Paulo, 01246-903 SP, Brazil.
  10. Emer S Ferro: Department of Pharmacology, Biomedical Sciences Institute, São Paulo 05508-000, Brazil.

Abstract

Intracellular peptides (InPeps) generated by the orchestrated action of the proteasome and intracellular peptidases have biological and pharmacological significance. Here, human plasma relative concentration of specific InPeps was compared between 175 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and 45 SARS-CoV-2 non-infected patients; 2,466 unique peptides were identified, of which 67% were InPeps. The results revealed differences of a specific group of peptides in human plasma comparing non-infected individuals to patients infected by SARS-CoV-2, following the results of the semi-quantitative analyses by isotope-labeled electrospray mass spectrometry. The protein-protein interactions networks enriched pathways, drawn by genes encoding the proteins from which the peptides originated, revealed the presence of the coronavirus disease/COVID-19 network solely in the group of patients fatally infected by SARS-CoV-2. Thus, modulation of the relative plasma levels of specific InPeps could be employed as a predictive tool for disease outcome.

Keywords

References

  1. Science. 2020 Mar 13;367(6483):1260-1263 [PMID: 32075877]
  2. Clin Proteomics. 2018 Dec 01;15:39 [PMID: 30519149]
  3. Bioinformatics. 2012 Jan 15;28(2):288-9 [PMID: 22113085]
  4. Nat Commun. 2022 Feb 16;13(1):888 [PMID: 35173144]
  5. EClinicalMedicine. 2021 Jun;36:100883 [PMID: 33969282]
  6. Viruses. 2022 Apr 25;14(5): [PMID: 35632633]
  7. Nat Commun. 2019 Mar 18;10(1):1240 [PMID: 30886144]
  8. Front Genet. 2019 Sep 25;10:858 [PMID: 31608109]
  9. JAMA Neurol. 2020 Jun 1;77(6):683-690 [PMID: 32275288]
  10. Signal Transduct Target Ther. 2023 Feb 27;8(1):84 [PMID: 36849525]
  11. EBioMedicine. 2022 Nov;85:104293 [PMID: 36182629]
  12. Eur J Neurol. 2023 May;30(5):1272-1280 [PMID: 36807419]
  13. Thromb Res. 1994 Jul 15;75(2):195-202 [PMID: 7974393]
  14. Mol Biosyst. 2012 Jan;8(1):268-81 [PMID: 21909575]
  15. Biomolecules. 2019 Apr 16;9(4): [PMID: 30995799]
  16. J Clin Invest. 2004 Jul;114(1):104-11 [PMID: 15232617]
  17. Sci Rep. 2021 Jul 27;11(1):15223 [PMID: 34315957]
  18. Sci Signal. 2021 Jan 12;14(665): [PMID: 33436497]
  19. ACS Cent Sci. 2021 Jan 27;7(1):156-163 [PMID: 33527085]
  20. Science. 1997 Dec 19;278(5346):2075-80 [PMID: 9405336]
  21. Nat Rev Drug Discov. 2003 Sep;2(9):703-16 [PMID: 12951577]
  22. Sci Rep. 2022 Jan 24;12(1):1212 [PMID: 35075175]
  23. Acta Pharmacol Sin. 2020 Sep;41(9):1141-1149 [PMID: 32747721]
  24. J Proteomics. 2017 Jan 16;151:74-82 [PMID: 27523479]
  25. AAPS J. 2010 Dec;12(4):608-16 [PMID: 20665142]
  26. Nat Immunol. 2022 Feb;23(2):186-193 [PMID: 35105982]
  27. Nature. 2021 Jun;594(7862):240-245 [PMID: 33979833]
  28. Trends Pharmacol Sci. 2022 Mar;43(3):234-248 [PMID: 34911657]
  29. Lancet Digit Health. 2022 Oct;4(10):e727-e737 [PMID: 36057526]
  30. Bioinformatics. 2015 Dec 15;31(24):3997-9 [PMID: 26315911]
  31. Biomed Res Int. 2021 Jul 6;2021:9939134 [PMID: 34307679]
  32. Cell. 2021 Apr 1;184(7):1895-1913.e19 [PMID: 33657410]
  33. Circulation. 1997 Mar 4;95(5):1115-8 [PMID: 9054837]
  34. J Infect. 2020 Sep;81(3):e41-e43 [PMID: 32603675]
  35. Pharmaceutics. 2021 Sep 02;13(9): [PMID: 34575464]
  36. EMBO J. 2005 Apr 20;24(8):1634-43 [PMID: 15791205]
  37. Bioorg Med Chem. 2018 Jun 1;26(10):2700-2707 [PMID: 28720325]
  38. J Proteomics. 2017 Jan 16;151:24-32 [PMID: 27371349]
  39. Mol Cell Proteomics. 2017 Dec;16(12):2055-2068 [PMID: 28982716]
  40. Int J Mol Sci. 2018 Mar 07;19(3): [PMID: 29518939]
  41. J Mol Cell Cardiol. 1999 Jan;31(1):51-60 [PMID: 10072715]
  42. Int J Mol Sci. 2021 Aug 17;22(16): [PMID: 34445532]
  43. J Neurochem. 2010 May;113(4):871-80 [PMID: 20202081]
  44. Cell. 2011 Mar 18;144(6):986-98 [PMID: 21414488]
  45. Drug Discov Today. 2021 Jun;26(6):1521-1531 [PMID: 33524603]
  46. Cell Death Discov. 2021 Nov 12;7(1):351 [PMID: 34772908]
  47. Int Rev Neurobiol. 2022;165:63-89 [PMID: 36208907]
  48. Comput Struct Biotechnol J. 2021;19:1838-1847 [PMID: 33758649]
  49. Front Immunol. 2020 Dec 10;11:598444 [PMID: 33362782]
  50. J Infect. 2020 Aug;81(2):318-356 [PMID: 32283163]
  51. Sci Rep. 2019 May 21;9(1):7635 [PMID: 31114012]
  52. Nature. 2021 Jan;589(7840):125-130 [PMID: 32906143]
  53. Lancet Infect Dis. 2020 Aug;20(8):e192-e197 [PMID: 32539990]
  54. Biomolecules. 2020 Feb 17;10(2): [PMID: 32079362]
  55. Blood. 2020 Sep 10;136(11):1317-1329 [PMID: 32573711]
  56. Nucleic Acids Res. 2019 Jan 8;47(D1):D442-D450 [PMID: 30395289]
  57. Mol Cell. 2020 Oct 1;80(1):164-174.e4 [PMID: 32877642]
  58. J Biol Chem. 2014 Jun 13;289(24):16711-26 [PMID: 24764300]
  59. Bioinformatics. 2007 Apr 15;23(8):980-7 [PMID: 17303618]
  60. Mol Cell. 2016 Oct 6;64(1):12-23 [PMID: 27716480]
  61. Nat Commun. 2021 Nov 19;12(1):6761 [PMID: 34799561]
  62. Front Cardiovasc Med. 2023 Jan 06;9:1054690 [PMID: 36684608]
  63. Br J Nutr. 2000 Nov;84 Suppl 1:S99-102 [PMID: 11242453]
  64. Nat Cancer. 2023 May;4(5):629-647 [PMID: 37217651]
  65. Nucleic Acids Res. 2022 Jan 7;50(D1):D497-D508 [PMID: 34718738]
  66. Mol Biol Rep. 2022 Mar;49(3):2303-2309 [PMID: 35076845]
  67. PLoS One. 2016 Jan 27;11(1):e0147297 [PMID: 26815288]
  68. Bioinformatics. 2012 Nov 1;28(21):2856-7 [PMID: 22954629]
  69. Immunity. 2002 Sep;17(3):251-63 [PMID: 12354379]
  70. Reumatol Clin (Engl Ed). 2020 Nov - Dec;16(6):455-461 [PMID: 30594439]
  71. Signal Transduct Target Ther. 2021 Mar 6;6(1):110 [PMID: 33677468]
  72. Nucleic Acids Res. 2020 Jan 8;48(D1):D1145-D1152 [PMID: 31686107]
  73. Annu Rev Pharmacol Toxicol. 2020 Jan 6;60:457-476 [PMID: 31479618]
  74. Clin Transl Immunology. 2021 Mar 18;10(3):e1240 [PMID: 33747508]
  75. PLoS One. 2016 Sep 29;11(9):e0163312 [PMID: 27685651]
  76. Proteomics Clin Appl. 2018 Sep;12(5):e1700163 [PMID: 29611317]
  77. Genes Dev. 2000 May 1;14(9):1027-47 [PMID: 10809663]
  78. Signal Transduct Target Ther. 2017;2: [PMID: 29158945]

Word Cloud

Created with Highcharts 10.0.0peptidespatientsInPepsSARS-CoV-2plasmaspecificinfectedIntracellularhumanrelativecoronavirus2non-infectedresultsrevealedgroupgeneratedorchestratedactionproteasomeintracellularpeptidasesbiologicalpharmacologicalsignificanceconcentrationcompared175severeacuterespiratorysyndrome45466uniqueidentified67%differencescomparingindividualsfollowingsemi-quantitativeanalysesisotope-labeledelectrospraymassspectrometryprotein-proteininteractionsnetworksenrichedpathwaysdrawngenesencodingproteinsoriginatedpresencedisease/COVID-19networksolelyfatallyThusmodulationlevelsemployedpredictivetooldiseaseoutcomeSARS-CoV-2-infectedMicrobiologyPublichealthVirology

Similar Articles

Cited By

No available data.