Metabolic differences in delirium prone patients lead to a protein with computationally shown possibility for binding to Sars-CoV2 spike protein.

Delirium is an acute change in attention, awareness and cognition occurring as a result of medications, substance abuse, illness or surgery. Even routine surgical procedures can lead to delirium in some patients. Although patients generally recover after this post-operative delirium, it is a signal of brain vulnerability that makes these patients more likely to develop dementia later in life. Delirium has also been observed in ~65% of severe SARS-CoV-2 cases. Analysis of the metabolic characteristics of patients that develop post-operative delirium uncovered a link with Monoamine Oxidase B (MAOB), a known target for Parkinson’s disease therapy. MAOB is a mitochondrial membrane bound protein particularly important for the metabolism of neuroactive metabolites, one of the regulators of platelet activity as well as nitric oxide synthases. Computational analysis showed major regional similarities between MAOB and ACE2 protein, major target for SARS-CoV2 spike protein. Our computational protein-protein docking analysis led us to propose a hypothetical relationship between MAOB and the SARS-CoV-2 spike protein hypothesizing possible effect on MAOB function in COVID-19 infection. In the future we will further explore relationship between delirium, viral infection and dementias.

Figure shows energetically preferred binding location for Spike proteins to MAOB dimer (Schrodinger Inc.). Approximate location of the membrane bilayer is indicated with a gray line. Shown are Spike proteins, MAOB chains as well as FAD - flavin adenine dinucleotide cofactor.