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Relationship between COVID-19 infection and neurodegeneration: Computational insight into interactions between the SARS-CoV-2 spike protein and the monoamine oxidase enzymes

View ORCID ProfileLucija Hok, View ORCID ProfileHrvoje Rimac, View ORCID ProfileJanez Mavri, View ORCID ProfileRobert Vianello
doi: https://doi.org/10.1101/2021.08.30.458208
Lucija Hok
1Laboratory for the Computational Design and Synthesis of Functional Materials, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia
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Hrvoje Rimac
2Department of Medicinal Chemistry, University of Zagreb Faculty of Pharmacy and Biochemistry, Zagreb, Croatia
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Janez Mavri
3Laboratory for Biocomputing and Bioinformatics, National Institute of Chemistry, Ljubljana, Slovenia
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Robert Vianello
1Laboratory for the Computational Design and Synthesis of Functional Materials, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia
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  • For correspondence: robert.vianello@irb.hr
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ABSTRACT

Although COVID-19 has been primarily associated with pneumonia, recent data show that its causative agent, the SARS-CoV-2 coronavirus, can infect many vital organs beyond the lungs, including the heart, kidneys and the brain. The literature agrees that COVID-19 is likely to have long-term mental health effects on infected individuals, which signifies a need to understand the role of the virus in the pathophysiology of brain disorders that is currently unknown and widely debated. Our docking and molecular dynamic simulations show that the affinity of the spike protein from the wild type (WT) and the South African B.1.351 (SA) variant towards the MAO enzymes is comparable to that for its ACE2 receptor. This allows for the WT/SA…MAO complex formation, which changes MAO affinities for their neurotransmitter substrates, thus consequently impacting the rates of their metabolic conversion and misbalancing their levels. Knowing that this fine regulation is strongly linked with the etiology of various brain pathologies, these results are the first to highlight the possibility that the interference with the brain MAO catalytic activity is responsible for the increased neurodegenerative illnesses following a COVID-19 infection, thus placing a neurobiological link between these two conditions in the spotlight. Since the obtained insight suggests that a more contagious SA variant causes even larger disturbances, and with new and more problematic strains likely emerging in the near future, we firmly advise that the presented prospect of the SARS-CoV-2 induced neurological complications should not be ignored, but rather requires further clinical investigations to achieve an early diagnosis and timely therapeutic interventions.

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TABLE OF CONTENTS ENTRYDocking and molecular dynamic simulations highlight the possibility that the interference with the brain monoamine oxidase (MAO) catalytic activity is responsible for the increased neurodegenerative illnesses following a COVID-19 infection.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 31, 2021.
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Relationship between COVID-19 infection and neurodegeneration: Computational insight into interactions between the SARS-CoV-2 spike protein and the monoamine oxidase enzymes
Lucija Hok, Hrvoje Rimac, Janez Mavri, Robert Vianello
bioRxiv 2021.08.30.458208; doi: https://doi.org/10.1101/2021.08.30.458208
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Relationship between COVID-19 infection and neurodegeneration: Computational insight into interactions between the SARS-CoV-2 spike protein and the monoamine oxidase enzymes
Lucija Hok, Hrvoje Rimac, Janez Mavri, Robert Vianello
bioRxiv 2021.08.30.458208; doi: https://doi.org/10.1101/2021.08.30.458208

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