The Potential Functions of Protein Domains during COVID Infection: An Analysis and a Review

Sobhy, Haitham

doi:10.3390/covid1010032

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…For example, HIV-1 imitates microtubular end-binding protein 1 (EB1), disrupting cognition directly ( Naghavi, 2021 ). Other viruses, including Influenza A and Zika, exploit the host microtubular network, while SARS-CoV-2 may accomplish the same via a tubulin-like MREL motif located in the NSP1 protein ( Simpson and Yamauchi, 2020 ; Sobhy, 2021 ).…”

Section: Cell-cell Fusion In Neuropsychiatric Disordersmentioning

confidence: 99%

“…The SARS-CoV-2 S protein was demonstrated to activate HERV-W-ENV gene in T lymphocytes, a protein associated with Alzheimer’s disease ( Balestrieri et al., 2021 ; Licastro and Porcellini, 2021 ). Another case of molecular mimicry was found between the SARS-CoV-2 NSP-1 antigen and host tubulin, likely connecting this virus to dysfunctional information processing ( Sobhy, 2021 ).…”

Section: Cell-cell Fusion the Molecular Actorsmentioning

confidence: 99%

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Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Osorio

Sfera

Anton

et al. 2022

Front. Cell. Infect. Microbiol.

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A growing body of epidemiological and research data has associated neurotropic viruses with accelerated brain aging and increased risk of neurodegenerative disorders. Many viruses replicate optimally in senescent cells, as they offer a hospitable microenvironment with persistently elevated cytosolic calcium, abundant intracellular iron, and low interferon type I. As cell-cell fusion is a major driver of cellular senescence, many viruses have developed the ability to promote this phenotype by forming syncytia. Cell-cell fusion is associated with immunosuppression mediated by phosphatidylserine externalization that enable viruses to evade host defenses. In hosts, virus-induced immune dysfunction and premature cellular senescence may predispose to neurodegenerative disorders. This concept is supported by novel studies that found postinfectious cognitive dysfunction in several viral illnesses, including human immunodeficiency virus-1, herpes simplex virus-1, and SARS-CoV-2. Virus-induced pathological syncytia may provide a unified framework for conceptualizing neuronal cell cycle reentry, aneuploidy, somatic mosaicism, viral spreading of pathological Tau and elimination of viable synapses and neurons by neurotoxic astrocytes and microglia. In this narrative review, we take a closer look at cell-cell fusion and vesicular merger in the pathogenesis of neurodegenerative disorders. We present a “decentralized” information processing model that conceptualizes neurodegeneration as a systemic illness, triggered by cytoskeletal pathology. We also discuss strategies for reversing cell-cell fusion, including, TMEM16F inhibitors, calcium channel blockers, senolytics, and tubulin stabilizing agents. Finally, going beyond neurodegeneration, we examine the potential benefit of harnessing fusion as a therapeutic strategy in regenerative medicine.

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Section: Cell-cell Fusion In Neuropsychiatric Disordersmentioning

confidence: 99%

Section: Cell-cell Fusion the Molecular Actorsmentioning

confidence: 99%

Virus-Induced Membrane Fusion in Neurodegenerative Disorders

Osorio

Sfera

Anton

et al. 2022

Front. Cell. Infect. Microbiol.

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“…Those highest mutations did not occur in the functional domain. 14,15 So, the purpose of this study is to look for other nonsynonymous mutations, which were found in Indonesia samples that occur in the functional domains of ORF3a SARS-CoV-2. Furthermore, we analyze the unique truncated protein of ORF3a SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

Unique truncated and non-synonymous mutations in functional domains of ORF3a SARS-CoV-2

Christian¹,

Yuliawuri²

2023

JMedScie

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Previous studies showed that mutations in the SARS-CoV-2 ORF3a protein can influence viral pathogenesis. Therefore, it is necessary to observe mutations, especially in the functional domain of the protein. We observed the presence of mutations in the ORF3a protein by analyzing 5,131 samples from the GISAID database since it was first discovered in March 2020 until November 2021. The sequence was aligned using Clustal Omega Multiple Sequence Alignment from EMBL-EBI and analyzed using BioEdit version 7.2.5 software using reference sequences NC045512. Samples having the letter N were omitted from the analysis. The effect of point mutations on proteins was analyzed using the Protein Variation Effect Analyzer (PROVEAN) v1.1.3 software. The functional domains of the ORF3a protein were visualized using RasWin software. We identified 312 mutations in the SARS-CoV-2 ORF3a protein. In addition, from 5,131 samples, 915 samples were found to be truncated in the C-terminal region of the protein. These non-synonymous mutations data in functional domains and truncated sequences indicate that amino acid changes in the ORF3a protein require further studies to determine the effect of viral pathogenicity in humans.

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