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

doi:10.1038/s41598-021-90243-1

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

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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 language	English
Article number	10629
Pages (from-to)	10629
Number of pages	14
Journal	Scientific Reports
Volume	11
Issue number	1
Early online date	20 May 2021
DOIs	https://doi.org/10.1038/s41598-021-90243-1 https://doi.org/10.1038/s41598-021-90243-1
Publication status	Published - 20 May 2021

Keywords

Aged
Aged, 80 and over
COVID-19/metabolism
Delirium/metabolism
Female
Humans
Male
Metabolomics
Monoamine Oxidase/metabolism
Spike Glycoprotein, Coronavirus/metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Metabolomics and computational analysis of the role of monoamine oxidase activity in delirium and SARS‑COV‑2 infection
© 2021 The Authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 2.97 MBLicence: CC BY

Metabolomic studies of human plasma and cerebrospinal fluid from an observational cohort study of orthopaedic patients investigating post-operative delirium
Jung, M. (Author), Cunningham, E. (Supervisor) & Green, B. (Supervisor), Jul 2023
Student thesis: Doctoral Thesis › Doctor of Philosophy

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Cuperlovic-Culf, M., Cunningham, E. L., Teimoorinia, H., Surendra, A., Pan, X., Bennett, S. A. L., Jung, M., McGuiness, B., Passmore, A. P., Beverland, D., & Green, B. D. (2021). Metabolomics and computational analysis of the role of monoamine oxidase activity in delirium and SARS-COV-2 infection. Scientific Reports, 11(1), 10629. Article 10629. https://doi.org/10.1038/s41598-021-90243-1, https://doi.org/10.1038/s41598-021-90243-1

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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{\textquoteright}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.",

keywords = "Aged, Aged, 80 and over, COVID-19/metabolism, Delirium/metabolism, Female, Humans, Male, Metabolomics, Monoamine Oxidase/metabolism, Spike Glycoprotein, Coronavirus/metabolism",

author = "Miroslava Cuperlovic-Culf and Cunningham, {Emma L} and Hossen Teimoorinia and Anuradha Surendra and Xiaobei Pan and Bennett, {Steffany A L} and Mijin Jung and Bernadette McGuiness and Passmore, {Anthony Peter} and David Beverland and Green, {Brian D}",

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Cuperlovic-Culf, M, Cunningham, EL, Teimoorinia, H, Surendra, A, Pan, X, Bennett, SAL, Jung, M, McGuiness, B, Passmore, AP, Beverland, D & Green, BD 2021, 'Metabolomics and computational analysis of the role of monoamine oxidase activity in delirium and SARS-COV-2 infection', Scientific Reports, vol. 11, no. 1, 10629, pp. 10629. https://doi.org/10.1038/s41598-021-90243-1, https://doi.org/10.1038/s41598-021-90243-1

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T1 - Metabolomics and computational analysis of the role of monoamine oxidase activity in delirium and SARS-COV-2 infection

AU - Cuperlovic-Culf, Miroslava

AU - Cunningham, Emma L

AU - Teimoorinia, Hossen

AU - Surendra, Anuradha

AU - Pan, Xiaobei

AU - Bennett, Steffany A L

AU - Jung, Mijin

AU - McGuiness, Bernadette

AU - Passmore, Anthony Peter

AU - Beverland, David

AU - Green, Brian D

PY - 2021/5/20

Y1 - 2021/5/20

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - COVID-19/metabolism

KW - Delirium/metabolism

KW - Female

KW - Humans

KW - Male

KW - Metabolomics

KW - Monoamine Oxidase/metabolism

KW - Spike Glycoprotein, Coronavirus/metabolism

U2 - 10.1038/s41598-021-90243-1

DO - 10.1038/s41598-021-90243-1

M3 - Article

C2 - 34017039

SN - 2045-2322

VL - 11

SP - 10629

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 10629

ER -

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

Abstract

Keywords

UN SDGs

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Student theses

Metabolomic studies of human plasma and cerebrospinal fluid from an observational cohort study of orthopaedic patients investigating post-operative delirium

Cite this