Metabolomics and computational analysis of the role of monoamine oxidase activity in delirium and SARS-COV-2 infection

Miroslava Cuperlovic-Culf*, Emma L. Cunningham, Hossen Teimoorinia, Anuradha Surendra, Xiaobei Pan, Steffany A. L. Bennett, Mijin Jung, Bernadette McGuiness, Anthony Peter Passmore, David Beverland, Brian D. Green*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Delirium is an acute change in attention and cognition occurring in ~ 65% of severe SARS-CoV-2 cases. It is also common following surgery and an indicator of brain vulnerability and risk for the development of dementia. In this work we analyzed the underlying role of metabolism in delirium-susceptibility in the postoperative setting using metabolomic profiling of cerebrospinal fluid and blood taken from the same patients prior to planned orthopaedic surgery. Distance correlation analysis and Random Forest (RF) feature selection were used to determine changes in metabolic networks. We found significant concentration differences in several amino acids, acylcarnitines and polyamines linking delirium-prone patients to known factors in Alzheimer’s disease such as monoamine oxidase B (MAOB) protein. Subsequent computational structural comparison between MAOB and angiotensin converting enzyme 2 as well as protein–protein docking analysis showed that there potentially is strong binding of SARS-CoV-2 spike protein to MAOB. The possibility that SARS-CoV-2 influences MAOB activity leading to the observed neurological and platelet-based complications of SARS-CoV-2 infection requires further investigation.
Original languageEnglish
Article number10629
Number of pages14
JournalScientific Reports
Volume11
Issue number1
Early online date20 May 2021
DOIs
Publication statusEarly online date - 20 May 2021

Keywords

  • Article
  • /631/114/2397
  • /631/114/2164
  • /692/617/375
  • /631/378/2611
  • article

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