Possible routes of SARS‐CoV‐2 invasion in brain: In context of neurological symptoms in COVID‐19 patients

Kumar, Ashutosh; Pareek, Vikas; Prasoon, Pranav; Faiq, Muneeb A.; Kumar, Pavan; Kumari, Chiman; Narayan, Ravi Kant

doi:10.1002/jnr.24717

Cited by 57 publications

(71 citation statements)

References 44 publications

(90 reference statements)

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“…Проявление неврологических симптомов у некоторых пациентов с COVID-19 представляет собой проблему для нейробиологов в виду недостаточно изученного патоморфогенеза [45].…”

Section: неврологческие проявления Covid-19 как предпосылки для изучеunclassified

“…В недавнем исследовании Song с соавт [78] показали широко распространенную экспрессию белка АПФ2 в нейронах и глиальных клетках перивентрикулярных образований головного мозга человека [45]. Они также показали, что SARS-CoV-2 может инфицировать структуры головного мозга, которые можно заблокировать с помощью антител, специфичных к АПФ2, или путем введения спинномозговой жидкости пациента с COVID-19, что указывает на ключевую роль АПФ2 в процессе инфицирования головного мозга [70].…”

Section: возможные пути и механизмы проникновения Sars-cov-2 в цнсunclassified

“…Присутствие вирусных рецепторов проникновения на клетках обонятельного эпителия, центральной и энтеральной нервной системы является основой для невральной инвазии SARS-CoV-2 через обонятельный и трансвагальный пути [45].…”

Section: возможные пути и механизмы проникновения Sars-cov-2 в цнсunclassified

“…В связи с этим недавно было показано, что SARS-CoV-2 реплицируется в энтероцитах человека [46]. У пациентов с COVID-19 обычно наблюдаются пищеварительные симптомы, указывающие на инфекцию [45,89].…”

Section: возможные пути и механизмы проникновения Sars-cov-2 в цнсunclassified

“…Вспышка SARS-CoV-2не первая эпидемия коронавируса (CoV), возникшая в XXI веке: в эту классификацию были включены как SARS-CoV 2002 г., так и коронавирус ближневосточного респираторного синдрома 2012 г. (MERS-CoV) [45,64]. По сравнению с другими коронавирусами (HCoV-229E, HCoV-OC43, HCoV-NL63), которые являются патогенными для человека, но проявляют лишь умеренно выраженные клинические симптомы, SARS-CoV-2 больше напоминает MERS-CoV и SARS-CoV по степени тяжести клинических проявлений и способности инфицировать не только дыхательные пути [53].…”

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Molecular and cellular mechanisms of central nervous system alteration in COVID-19

Алексеева

Sokolov

Никитюк

et al. 2020

Žurnal anatomii i gistopatologii

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The ongoing coronavirus disease 2019 (COVID-19) pandemic dictates the need to study the molecular and cellular mechanisms of interaction between the pathogen and the human body. The manifestation of neurological symptoms in some patients with COVID-19 is a problem for neuroscientists due to the insufficiently understood pathomorphogenesis of the disease. This review systematizes the literature data reflecting the ways of penetration of SARS-CoV-2 into the brain, features of its interaction with neurons, neuroglia, and immune cells. It has been shown that the main mechanisms of SARS-CoV-2 neuroinvasion are presumably retrograde axonal transport along the fibers of the olfactory and vagus nerves; penetration through the damaged blood-brain barrier (BBB) or migration of immunocompetent cells containing viral particles through the intact BBB. It was found that virusinducible neuronal death is caused not only by a direct cytotoxic effect, but also due to dysregulation of the reninangiotensin system of the brain and the release of a large amount of inflammatory cytokines as a manifestation of a “cytokine storm”. The participation of neuroglial cells in the initiation and maintenance of neuroinflammatory and neurodegenerative processes due to the activation of their proinflammatory phenotype has been demonstrated. The role of mast cells in antiviral defense mechanisms and inflammatory reactions is discussed.

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Section: неврологческие проявления Covid-19 как предпосылки для изучеunclassified

Section: возможные пути и механизмы проникновения Sars-cov-2 в цнсunclassified

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Molecular and cellular mechanisms of central nervous system alteration in COVID-19

Алексеева

Sokolov

Никитюк

et al. 2020

Žurnal anatomii i gistopatologii

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Computational Screening of Neuropilin‐1 Unveils Novel Potential Anti‐SARS‐CoV‐2 Therapeutics

Afiadenyo,

Adams,

Agoni

et al. 2023

Chemistry & Biodiversity

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Neuropilin 1 (NRP‐1) inhibition has shown promise in reducing the infectivity of severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) and preventing the virus entry into nerve tissues, thereby mitigating neurological symptoms in COVID‐19 patients. In this study, we employed virtual screening, including molecular docking, Molecular Dynamics (MD) simulation, and Molecular Mechanics‐Poisson Boltzmann Surface Area (MM‐PBSA) calculations, to identify potential NRP‐1 inhibitors. From a compendium of 1930 drug‐like natural compounds, we identified five potential leads: CNP0435132, CNP0435311, CNP0424372, CNP0429647, and CNP0427474, displaying robust binding energies of ‐8.2,‐8.1,‐10.7,‐8.2, and ‐8.2 kcal/mol, respectively. These compounds demonstrated interactions with critical residues Tyr297, Trp301, Thr316, Asp320, Ser346, Thr349, and Tyr353 located within the b1 subdomain of NRP‐1. Furthermore, MD simulations and MM‐PBSA calculations affirmed the stability of the complexes formed, with average root mean square deviation, radius of gyration, and solvent accessible surface area values of 0.118 nm,1.516 nmand 88.667nm² respectively. Notably, these lead compounds were estimated to penetrate the blood‐brain barrier and displayed antiviral properties, with Pa values ranging from 0.414 to 0.779. The antagonistic effects of these lead compounds merit further investigation, as they hold the potential to serve as foundational scaffolds for the development of innovative therapeutics aimed at reducing the neuroinfectivity of SARS‐CoV‐2.

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A review of ischemic stroke in COVID-19: currently known pathophysiological mechanisms

Tang

Zheng

2021

Neurol Sci

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Coronavirus disease 2019 (COVID-19), the third type of coronavirus pneumonia after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), is spreading widely worldwide now. This pneumonia causes not only respiratory symptoms but also multiple organ dysfunction, including thrombotic diseases such as ischemic stroke. The purpose of this review is to explore whether COVID-19 is a risk factor for ischemic stroke and its related pathophysiological mechanisms. Based on the high thrombosis rate and frequent strokes of COVID-19 patients, combined with related laboratory indicators and pathological results, the discussion is mainly from two aspects: nerve invasion and endothelial dysfunction. SARS-CoV-2 can directly invade the CNS through blood-borne and neuronal retrograde pathways, causing cerebrovascular diseases. In addition, the endothelial dysfunction in COVID-19 is almost certain. Cytokine storm causes thromboinflammation, and downregulation of ACE2 leads to RAS imbalance, which eventually lead to ischemic stroke.

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Possible routes of SARS‐CoV‐2 invasion in brain: In context of neurological symptoms in COVID‐19 patients

Cited by 57 publications

References 44 publications

Molecular and cellular mechanisms of central nervous system alteration in COVID-19

Molecular and cellular mechanisms of central nervous system alteration in COVID-19

Computational Screening of Neuropilin‐1 Unveils Novel Potential Anti‐SARS‐CoV‐2 Therapeutics

A review of ischemic stroke in COVID-19: currently known pathophysiological mechanisms

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