In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19

Elkazzaz, Mahmoud; Ahmed, Amr; Abo-Amer, Yousry Esam-Eldin; Hydara, Tamer; Haikal, Abdullah; Midan, Dina Abdel Razek; Eltayb, Wafa Ali; Wang, Xiling; Karpiński, Tomasz M.; Hamza, Dalia; Jabbar, Basit; Shamkh, Israa M

doi:10.3390/vaccines10091500

Cited by 8 publications

(1 citation statement)

References 28 publications

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“…Activation of GPCRs and GNRHRs are responsible for cortisol levels and the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), respectively. Inhibition of these receptors disrupts the neuroendocrine system and its effects on peripheral endocrine glands [ 157 ]. Furthermore, virus infiltration and cytokine effects impair the hormonal axis mentioned below.…”

Section: Covid-19 and The Endocrine Systemmentioning

confidence: 99%

The Latest Cellular and Molecular Mechanisms of COVID-19 on Non-Lung Organs

et al. 2023

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Understanding the transmission pathways of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will aid in developing effective therapies directed at the virus's life cycle or its side effects. While severe respiratory distress is the most common symptom of a coronavirus 2019 (COVID-19) infection, the virus is also known to cause damage to almost every major organ and system in the body. However, it is not obvious whether pathological changes in extra-respiratory organs are caused by direct infection, indirect, or combination of these effects. In this narrative review, we first elaborate on the characteristics of SARS-CoV-2, followed by the mechanisms of this virus on various organs such as brain, eye, and olfactory nerve and different systems such as the endocrine and gastrointestinal systems.

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Section: Covid-19 and The Endocrine Systemmentioning

confidence: 99%

The Latest Cellular and Molecular Mechanisms of COVID-19 on Non-Lung Organs

et al. 2023

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AI-driven Discovery of Celecoxib and Dexamethasone for Exploring their Mode of Action as Human Interleukin (IL-6) Inhibitors to Treat COVID-19-induced Cytokine Storm in Humans

Shamkh,

Elkazzaz,

Radwan

et al. 2023

CPD

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Background:: In the case of COVID-19 patients, it has been observed that the immune system of the infected person exhibits an extreme inflammatory response known as cytokine release syndrome (CRS) where the inflammatory cytokines are swiftly produced in quite large amounts in response to infective stimuli. Numerous case studies of COVID-19 patients with severe symptoms have documented the presence of higher plasma concentrations of human interleukin-6 (IL-6), which suggests that IL-6 is a crucial factor in the pathophysiology of the disease. In order to prevent CRS in COVID-19 patients, the drugs that can exhibit binding interactions with IL-6 and block the signaling pathways to decrease the IL-6 activity may be repurposed. Methods:: This research work focused on molecular docking-based screening of the drugs celecoxib (CXB) and dexamethasone (DME) to explore their potential to interact with the binding sites of IL-6 protein and reduce the hyper-activation of IL-6 in the infected personnel. Results:: Both of the drugs were observed to bind with the IL-6 (IL-6 receptor alpha chain) and IL-6Rα receptor with the respective affinities of -7.3 kcal/mol and -6.3 kcal/mol, respectively, for CXB and DME. Moreover, various types of binding interactions of the drugs with the target proteins were also observed in the docking studies. The dynamic behaviors of IL-6/IL-6Rα in complex with the drugs were also explored through molecular dynamics simulation analysis. The results indicated significant stabilities of the acquired drug-protein complexes up to 100 ns. Conclusion:: The findings of this study have suggested the potential of the drugs studied to be utilized as antagonists for countering CRS in COVID-19 ailment. This study presents the studied drugs as promising candidates both for the clinical and pre-clinical treatment of COVID-19.

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Staunch the Age Related Decline into Dementia, Cancer, Autoimmunity (Long Covid), Obesity, and Other Diseases with a Prebiotic, Probiotic, Postbiotic Triple Play

Chambers

2024

Preprint

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“All diseases originate in the gut.” Hippocrates (400 BC) A healthy gut microbiome via the gut-brain-axis (GBA) elevates heart rate variability (HRV), a general measure of health and well-being. A dysbiotic gut microbiome, low in biodiversity and butyrate producers, alters tryptophan metabolism with release of proinflammatory cytokines, predominantly TNF-α, IL-6, and IL-1β. These also characterize chronic inflammation, oxidative stress, and a multitude of diseases, all exhibiting low HRV. Gut dysbiosis upregulates IFN-γ and with it IDO (indoleamine 2,3 dioxygenase). Tryptophan pivots from serotonin synthesis to that of IDO induced kynurenine, increasing the kynurenine to tryptophan ratio (KTR). An elevated KTR is positively linked to neurodegenerative and autoimmune diseases and negatively linked to HRV. Elevated IDO activity is not only enzymatic but also an intracellular signal transducer potentiated by TGF-β. This cytokine is the primary determinant of the TME. Also proposed is the gut-lung dysbiosis concept and consequent degradation of ACE2 (richest in lungs and gut). Leaky gut induced autoantibodies related to G-protein coupled receptors (GPCRs) in combination with increased Ang II further potentiate oxidative stress. Aldosterone and paroxysmal orthostatic tachycardia syndrome (POTS) paradoxes are highlighted in the context of GPCR and gut dysbiosis, and the role of Candida is explored. The efficacy of fecal microbiome transplantation (FMT) in treating dementia, cancer, and autoimmunity supports the plausibility of success with “FMT-lite”. This triple play of a prebiotic (d-mannose), probiotic (bifidobacteria and lactobacilli), and postbiotic (butyrate) might improve intestinal barrier integrity, oppose entry of GPCR antigens, suppress the inflammatory cytokine triad, balance IFN-γ and TGF-β, suppress oxidative stress, depress KTR, elevate HRV, and extend lifespan and its quality.

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In Silico Discovery of GPCRs and GnRHRs as Novel Binding Receptors of SARS-CoV-2 Spike Protein Could Explain Neuroendocrine Disorders in COVID-19

Cited by 8 publications

References 28 publications

The Latest Cellular and Molecular Mechanisms of COVID-19 on Non-Lung Organs

The Latest Cellular and Molecular Mechanisms of COVID-19 on Non-Lung Organs

AI-driven Discovery of Celecoxib and Dexamethasone for Exploring their Mode of Action as Human Interleukin (IL-6) Inhibitors to Treat COVID-19-induced Cytokine Storm in Humans

Staunch the Age Related Decline into Dementia, Cancer, Autoimmunity (Long Covid), Obesity, and Other Diseases with a Prebiotic, Probiotic, Postbiotic Triple Play

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