Abstract
The first clinical symptoms focused on the presentation of coronavirus disease 2019 (COVID-19) have been respiratory failure, however, accumulating evidence also points to its presentation with neuropsychiatric symptoms, the exact mechanisms of which are not well known. By using a computational methodology, we aimed to explain the molecular paths of COVID-19 associated neuropsychiatric symptoms, based on the mimicry of the human protein interactions with SARS-CoV-2 proteins.Methods: Available 11 of the 29 SARS-CoV-2 proteins’ structures have been extracted from Protein Data Bank. HMI-PRED (Host-Microbe Interaction PREDiction), a recently developed web server for structural PREDiction of protein-protein interactions (PPIs) between host and any microbial species, was used to find the “interface mimicry” through which the microbial proteins hijack host binding surfaces. Classification of the found interactions was conducted using the PANTHER Classification System.Results: Predicted Human-SARS-CoV-2 protein interactions have been extensively compared with the literature. Based on the analysis of the molecular functions, cellular localizations and pathways related to human proteins, SARS-CoV-2 proteins are found to possibly interact with human proteins linked to synaptic vesicle trafficking, endocytosis, axonal transport, neurotransmission, growth factors, mitochondrial and blood-brain barrier elements, in addition to its peripheral interactions with proteins linked to thrombosis, inflammation and metabolic control.Conclusion: SARS-CoV-2-human protein interactions may lead to the development of delirium, psychosis, seizures, encephalitis, stroke, sensory impairments, peripheral nerve diseases, and autoimmune disorders. Our findings are also supported by the previous in vivo and in vitro studies from other viruses. Further in vivo and in vitro studies using the proteins that are pointed here, could pave new targets both for avoiding and reversing neuropsychiatric presentations.
Highlights
First identified in December 2019, coronavirus disease 2019 (COVID-19) has been announced as a pandemic and as of August 26th, 2020, more than 23 million confirmed cases, and more than 815.000 confirmed deaths around 216 countries have been announced1.Accumulating evidence points to its presentation with neuropsychiatric symptoms
The list of involved proteins in each category has been investigated and additional proteins that could take part in these pathways and that could be responsible for the neuropsychiatric representations of SARS-CoV-2 have been added by the researchers, based on the lists presented by the PANTHER analysis, authors’ knowledge and literature search for the direct and indirect impact on the central nervous system (CNS), to generate the hypothesis
Of the 2256 genes that hit 1874 molecular functions, 33.1% showed a binding molecular activity, 30.1% was related to catalytic activity, whereas 2.8% was related to a transporter activity, based on the PANTHER classification (Figure 2A)
Summary
First identified in December 2019, coronavirus disease 2019 (COVID-19) has been announced as a pandemic and as of August 26th, 2020, more than 23 million confirmed cases, and more than 815.000 confirmed deaths around 216 countries have been announced1.Accumulating evidence points to its presentation with neuropsychiatric symptoms. Higher incidence of embolism (Poissy et al, 2020) and risk for coagulation (Xiong et al, 2020), ischemic and hemorrhagic stroke (Beyrouti et al, 2020; Ellul et al, 2020; Gonzalez-Pinto et al, 2020; Paterson et al, 2020), confusion, encephalopathy, and seizures (Hosseini et al, 2020; Karimi et al, 2020), ataxia, headache, dizziness, and sensory impairment (Herman et al, 2020; Mao et al, 2020), cranial neuropathies (Dinkin et al, 2020), decreased smell function (Moein et al, 2020) and anosmia (Boscolo-Rizzo et al, 2020; Hopkins et al, 2020; Lechien et al, 2020; Pallanti, 2020), decreased taste dysfunction (BoscoloRizzo et al, 2020) and encephalitis (McAbee et al, 2020), and parainfectious peripheral nerve-related effects as Guillain Barre (Ottaviani et al, 2020; Padroni et al, 2020; Paterson et al, 2020; Sedaghat and Karimi, 2020; Toscano et al, 2020; Zhao et al, 2020), and Miller Fisher syndromes (Gutierrez-Ortiz et al, 2020) have been reported as individual cases. Presentation with stroke in 3 patients, resembling antiphospholipid antibody syndrome, showed an increased risk for neural autoimmunity (Zhang et al, 2020)
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